Publications by authors named "Yanyun Wang"

140 Publications

A joint method for the screening of pharmacological chaperones for phenylalanine hydroxylase.

Org Biomol Chem 2021 Jun 11. Epub 2021 Jun 11.

The affiliated Obstetrics and Gynecology Hospital with Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Center of Genetic Medicine, Nanjing 210004, Jiangsu, P.R. China.

Phenylalanine hydroxylase (PAH) deficiency (PAHD) is an autosomal recessive disorder that causes severe injury to the nervous system, the treatment of which mainly depends on dietary therapy. The limited treatment options for PAHD are an incentive to develop new methods to identify more efficient therapeutic drugs, such as agonists which could improve PAH activity. In this study, we aimed to establish a rapid and convenient method for the screening and verification of PAH agonists. We compared fluorospectrophotometry and tandem mass spectrometry for detection of enzymatic formation of tyrosine, finding that the latter was a more sensitive method. We optimized immunoprecipitation purification conditions and measurement conditions of PAH activity. The optimal ratio between PAH protein and magnetic beads was 500 μg protein per 20 μL beads, and the optimized conditions for the detection of PAH enzymatic activity included the presence of 75 μM coenzyme ((6R)-l-erythro-5,6,7,8-tetrahydrobiopterin) and 30 min reaction time. Based on virtual screening, we screened ten candidate agonists from the FDA drug library. Three of these (nefopam, fluocinonide, and risperidone) were found to activate the enzyme in a dose-dependent manner (0.1-10 μM) by the joint method. We tested the efficacy of the three agonists on three PAH mutations (p.I65T, p.H107R, and p.D101N) that influence enzyme activity, and found that risperidone could specifically activate D101N-mutated enzyme. In conclusion, we established a joint method that is highly reliable, cost-effective, labor-saving, and time-saving. And we also found a specific agonist for D101N-mutated PAH by this joint method which may assist the development of clinical treatment for PAHD patients with different enzyme deficiencies.
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http://dx.doi.org/10.1039/d1ob00638jDOI Listing
June 2021

Magnetoresponsive nanozyme: magnetic stimulation on the nanozyme activity of iron oxide nanoparticles.

Sci China Life Sci 2021 Apr 27. Epub 2021 Apr 27.

Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, 710127, China.

The iron oxide nanoparticles (IONPs) that combine the nanozyme activity and magnetothermal properties have attracted significant interest for various biomedical applications. However, the effect of magnetic stimulation in fine-tuning the nanozyme activities remains unclear. Here, we have constructed a series of IONPs with different magneto-thermal conversion abilities, and systematically study the effect of magnetic field stimulation on the peroxidase (POD) activity of IONPs. The results show that POD activity is effectively amplified via an in situ alternating magnetic field (AMF) stimulation with no solution temperature rise, and the degree of activity enhancement is closely related to the magnetic heating ability of the IONPs, confirming the origin of activity enhancement arises from the local magnetothermal effect. As the first report to prove magnetothermal regulation on nanozyme activity and to shed lights on the underlying correlation between activity enhancement and the intrinsic specific absorption rate (SAR), this work is expected to provide important support for future design of new magnetoresponsive nanozymes in various practical applications.
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http://dx.doi.org/10.1007/s11427-020-1907-6DOI Listing
April 2021

Adaptive immunity profiling associated with histological subtypes and postoperative survival in gastric cancer.

J Gastrointest Oncol 2021 Apr;12(2):328-343

Rehabilitation Department, Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.

Background: In gastric cancer (GC), abnormal adaptive immunity is correlated with chronic inflammatory disorders and poor prognosis. However, the global study of adaptive immunity involving genes expression is insufficient.

Methods: In this study, we investigated the transcriptional profile of adaptive immunity involving genes in GC from TCGA (The Cancer Genome Atlas). The relevance of adaptive immunity and the clinical features of patients with GC were assessed. Differences in gene expression between each feature and the correlation between gene expression and prognosis were elucidated.

Results: According to the expressional profile of adaptive immunity-related genes, 412 patients with GC were grouped into two primary classifications and three secondary classifications. There were no differences in prognosis detected between each subgroup. In the immune subgroups, the distributions of pathological type were obviously different. Additionally, histological types, AJCC (American Joint Committee on Cancer) stage features, grade, tumor stage, aneuploidy score, and fraction genome altered in different subgroups were significantly discrepant. There were 95 differently expressed genes (DEGs) detected between each histological type, which were represented by , and . According to identification of DEGs in the MSTAD (mucinous stomach adenocarcinoma) and SRCC (signet ring cell carcinoma) types, which were relevant to the best and worst prognosis types, respectively, we constructed a model combining seven genes to recognize the MSTAD type (AUC =0.91) and a model combining six genes to recognize the SRCC type (AUC =0.91). Moreover, the expression of gene was notably contrasting among the different histological types, and the high-expression of was correlated with a poor prognosis.

Conclusions: This study showed that the expressional patterns of adaptive immunity-related genes are closely related to the histological type of GC, and demonstrated that the expression of immune molecules is correlated to the prognosis. Our results are expected to promote immunological therapy for GC.
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http://dx.doi.org/10.21037/jgo-21-79DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107599PMC
April 2021

Neonatal screening and genotype-phenotype correlation of hyperphenylalaninemia in the Chinese population.

Orphanet J Rare Dis 2021 May 12;16(1):214. Epub 2021 May 12.

Genetic Medicine Center, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, 123 Tianfei St., Qinhuai District, Nanjing, 210004, People's Republic of China.

Background: Hyperphenylalaninemia (HPA) is the most common amino acid metabolic disease involving phenylalanine hydroxylase (PAH, OMIM*612,349) deficiency or coenzyme tetrahydrobiopterin (BH4) deficiency. Patients with severe HPA often have a difficult life. Early diagnosis of HPA before the development of symptoms is possible via neonatal screening, facilitating appropriate treatment and reducing mortality and disability rates. This study revealed the prevalence, mutational and phenotypic spectrum, and prognosis of HPA by neonatal screening from January 2001 to September 2020 in Nanjing, Jiangsu Province, China.

Methods: Through a retrospective analysis of the information available in the neonatal screening database, the clinical presentations, laboratory data, molecular characteristics and treatment follow-up data of HPA patients detected by neonatal screening were evaluated.

Results: We diagnosed 181 patients with HPA from 1 to 957 newborns, giving an incidence of 1:6873. Among these patients, 177 were identified as PAH deficient and four patients were BH4 deficient. The average current age of the patients was 6.38 years old. The most common mutations of PAH were c.728 C > A/ p.Arg243Gln (13.83 %), c.158G > A/ p.Arg53His (9.57 %), c.611 A > G/ p.Tyr204Cys (7.44 %), and c.721 C > T/ p.Arg241Cys (6.38 %).

Conclusions: This study revealed the prevalence, phenotype-genotype, and prognosis of HPA in China and contributes to the updating of PAHD data for China and worldwide. Our study not only expanded the spectrum of phenotypes and genotype but also provided a valuable tool for improved genetic counseling and management of future cases.
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http://dx.doi.org/10.1186/s13023-021-01846-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114530PMC
May 2021

An Easily Overlooked Contamination of Syringes in Newborn Screening by Tandem Mass Spectrometry.

Front Pediatr 2020 21;8:596321. Epub 2021 Jan 21.

Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China.

Tandem mass spectrometry becomes a common and important test in newborn screening, but potential contamination of the equipment has largely been ignored. The source of contamination through Biosan quality control samples was examined prospectively, and further confirmed by retrospective analysis of patient samples. We found that the source of contamination came from a syringe in the Biosan quality control samples. Furthermore, we found that a large number of indicators in the patient sample were interfered by syringe contamination in our center, and also in two other newborn screening centers, but the affected indicators were different in different screening centers. Syringe contamination will affect the detection of patient samples by tandem mass spectrometry and should be monitored carefully and immediately.
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http://dx.doi.org/10.3389/fped.2020.596321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861201PMC
January 2021

Neonatal Screening and Genotype-Phenotype Correlation of 21-Hydroxylase Deficiency in the Chinese Population.

Front Genet 2020 22;11:623125. Epub 2021 Jan 22.

Genetic Medicine Center, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders encompassing enzyme deficiencies in the adrenal steroidogenesis pathway that leads to impaired cortisol biosynthesis. 21-hydroxylase deficiency (21-OHD) is the most common type of CAH. Severe cases of 21-OHD may result in death during the neonatal or infancy periods or sterility in later life. The early detection and timely treatment of 21-OHD are essential. This study aimed to summarize the clinical and genotype characteristics of 21-OHD patients detected by neonatal screening in Nanjing, Jiangsu province of China from 2000 to 2019. Through a retrospective analysis of medical records, the clinical presentations, laboratory data, and molecular characteristics of 21-OHD patients detected by neonatal screening were evaluated. Of the 1,211,322 newborns who were screened, 62 cases were diagnosed with 21-OHD with an incidence of 1:19858. 58 patients were identified with the classical salt-wasting type (SW) 21-OHD and four patients were identified with simple virilizing type (SV) 21-OHD. Amongst these patients, 19 cases patients accepted genetic analysis, and another 40 cases were received from other cities in Eastern China. Eighteen different variants were found in the gene. The most frequent variants was c.293-13A/C>G (36.29%). The most severe clinical manifestations were caused by large deletions or conversions of . This study suggested that neonatal screening effectively leads to the early diagnosis of 21-OHD and reduces fatal adrenal crisis. Our data provide additional information on the occurrence and genotype-phenotype correlation of 21-OHD in the Chinese population which can be used to better inform treatment and improve prognosis.
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http://dx.doi.org/10.3389/fgene.2020.623125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862715PMC
January 2021

C-C Bond Cleavage Initiated Cascade Reaction of β-Enaminones: One-Pot Synthesis of 5-Hydroxy-1-pyrrol-2(5)-ones.

J Org Chem 2021 Feb 13;86(3):2917-2928. Epub 2021 Jan 13.

School of Environment and Public Health, Xiamen Key Laboratory of Food and Drug Safety, Xiamen Huaxia University, Xiamen, Fujian 361024, China.

An unprecedented C(CO)-C(Ar) bond cleavage of β-enaminones has been realized under mild and transition-metal-free conditions. The cascade transformation based on this C-C bond cleavage involves 1,3-O/C migration and aerobic hydroxylation and leads to various 5-hydroxy-1-pyrrol-2(5)-ones with broad functional group tolerance. The application of this methodology has been showcased by preparing 5-alkoxy-1-pyrrol-2(5)-one derivatives and a pyrrolo[2,1-]isoquinolin-3-one derivative.
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http://dx.doi.org/10.1021/acs.joc.0c02832DOI Listing
February 2021

Influence of indications on perinatal outcomes after radio frequency ablation in complicated monochorionic pregnancies: a retrospective cohort study.

BMC Pregnancy Childbirth 2021 Jan 9;21(1):41. Epub 2021 Jan 9.

Department of Obstetrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.

Background: Radiofrequency ablation (RFA) is recommended to prevent potential neurological injury or intrauterine foetal death (IUFD) of the co-twin(s) in complicated monochorionic (MC) pregnancies. However, the impacts of various indications on the pregnancy outcome following RFA remain unclear. This study aimed to determine how the indications influence the perinatal outcomes in complicated MC pregnancies undergoing radiofrequency ablation.

Methods: This was a retrospective cohort study performed in a single centre. All consecutive MC pregnancies treated with RFA between July 2011 and July 2019 were included. The adverse perinatal outcomes and the survival rate were analysed based on various indications. The continuous variables with and without normal distribution were compared between the groups using Student's t-test and Mann-Whitney U test, respectively, and for categorical variables, Chi-square and Fisher's exact tests were used. P < 0.05 indicated a significant difference.

Results: We performed 272 RFA procedures in 268 complicated MC pregnancies, including 60 selective intrauterine growth restriction (sIUGR), 64 twin-twin transfusion syndrome (TTTS), 12 twin reversed arterial perfusion sequence (TRAPs), 66 foetal anomaly and 66 elective foetal reduction (EFR) cases. The overall survival rate of the co-twin was 201/272 (73.9%). The overall technical successful rate was determined at 201/263 (76.7%). The IUFD rate in the co-twin was 20/272 (7.4%). The TTTS group had recorded the lowest survival rate (37/64, 57. 8%), and the survival rate was significantly correlated with Quintero stages (P = 0.029). Moreover, the sIUGR III subgroup had a lower survival rate compared with sIUGR II (55.6%, versus 84.3%). The subgroup of foetal anomaly of gastroschisis or exomphalos had the highest IUFD rate (4/10, 40%), followed by sIUGR III (2/9, 22.2%) and dichorionic triamniotic (DCTA) subgroup (8/46, 17.9%). In EFR group, eight IUFD cases were all coming from the DCTA subgroup and received RFA before 17 weeks.

Conclusions: The perinatal outcome of RFA was correlated with the indications, with the lowest survival rate in TTTS IV and the highest IUFD incidence in abdominal wall defect followed by sIUGR III. Elective RFA after 17 weeks may prevent IUFD in DCTA pregnancies.
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http://dx.doi.org/10.1186/s12884-020-03530-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797138PMC
January 2021

Lam and its Therapeutic Effects in Immune Disorders.

Front Pharmacol 2020 17;11:566783. Epub 2020 Dec 17.

Laboratory of Molecular Translational Medicine, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.

Lam., a plant native to tropical forests of India, is characterized by its versatile application as a food additive and supplement therapy. Accumulating evidence shows that plays a critical role in immune-related diseases. In this review, we cover the history, constituents, edibility, and general medicinal value of Moringa. The effects of Moringa in treating immune disorders are discussed in detail. Moringa can not only eliminate pathogens, including bacteria, fungi, viruses, and parasites, but also inhibit chronic inflammation, such as asthma, ulcerative colitis, and metabolic diseases. Additionally, Moringa can attenuate physical and chemical irritation-induced immune disorders, such as metal intoxication, drug side effects, or even the adverse effect of food additives. Autoimmune diseases, like rheumatoid arthritis, atopic dermatitis, and multiple sclerosis, can also be inhibited by Moringa. Collectively, Moringa, with its multiple immune regulatory bioactivities and few side effects, has a marked potential to treat immune disorders.
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http://dx.doi.org/10.3389/fphar.2020.566783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773658PMC
December 2020

Determination of ultra-low U in environment samples using ICP-MS/MS measurement and chemical separation.

Talanta 2021 Mar 11;224:121882. Epub 2020 Nov 11.

Xi'an AMS Center, State Key Laboratory of Loess and Quaternary Geology, Shaanxi Key Laboratory of AMS Technology and Application, Institute of Earth Environment, CAS, Xi'an, 710061, China.

U in the environment mainly originates from human nuclear activities. Based on the unique properties of uranium, U can be used as a powerful tracer for investigation of oceanographic and environmental processes. This requires sensitive measuement of U in various environmental samples. Due to the ultra-low radioactive level of U in the environment, its measurement is only possible by mass spectrometry. Because of the low atomic ratio of U/U down to 10-10 in the environment, the interferences of UH and peak tailings of U and U are critical challenges in the measurement of U by ICP-MS. This work developed a sensitive ICP-MS/MS method for measurement of ultra-low U by employing reaction cell technique and sequential quadrupole mass separators. By using 0.6 mL min CO - 7 mL min helium as collision/reaction gas to convert U and UH to UO, the interferences of UH (UOH/UO ratio) were significantly reduced to less than 2.4 × 10. A minimum detectable U/U ratio of 3.0 × 10 was achieved, which is one order of magnitude better than reported values. By using collision focusing with helium in the reaction cell and APEX sample introduction system, the measurement sensitivity for U (UO) was improved to 7.5 × 10 cps ppb. In combination with an effective chemical separation of uranium from sample matrix and interferences using total borate fusion following extraction chromatography with UTEVA resin, a detection limit of 7.2 × 10 g g for U was achieved. The developed method was verified by analysis of certified reference materials and by comparison with AMS measurement method. Soil samples collected from Northwest China were successfully analyzed. U/U ratios down to 9 × 10 were measured in these samples, and the sources of U in different sits were discussed.
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http://dx.doi.org/10.1016/j.talanta.2020.121882DOI Listing
March 2021

Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry and Rapid Evaporative Ionization Mass Spectrometry Were Used to Develop a Lamb Authentication Method: A Preliminary Study.

Foods 2020 Nov 24;9(12). Epub 2020 Nov 24.

Key Laboratory of Agro-food Safety and Quality, Institute of Quality Standard & Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Ministry of Agriculture and Rural Affairs, Beijing 100081, China.

A untargeted metabolomics approach was proposed in this study based on ultra-high performance liquid chromatography quadrupole time-of-flight (UHPLC-QTOF) and rapid evaporative ionization mass spectrometry (REIMS) to discriminate lamb and mutton meat and investigate their subtle metabolic differences, considering the higher popularity of lamb meat than mutton in the market. Multivariate statistical analysis was performed for data processing in order to distinguish between the two sample types. A total of 42 potential metabolites (20 in positive and 22 in negative ion mode) were defined for UHPLC-QTOF analysis, which provided references for discriminating the two kinds of meat. Furthermore, three potential markers were tentatively identified using LC/MS data against chemical databases. In addition, 14 potential metabolites were putatively identified in negative ion mode using the LipidMaps database. Meanwhile, the data-driven soft independent modeling of class analogy (DD-SIMCA) model was established, which could rapidly differentiate non-pretreated lamb meat and mutton with 92% specificity, rendering REIMS a promising technique for meat identification.
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http://dx.doi.org/10.3390/foods9121723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761048PMC
November 2020

Meat differentiation between pasture-fed and concentrate-fed sheep/goats by liquid chromatography quadrupole time-of-flight mass spectrometry combined with metabolomic and lipidomic profiling.

Meat Sci 2021 Mar 16;173:108374. Epub 2020 Nov 16.

Institute of Quality Standard & Testing Technology for Agro-Products, Key Laboratory of Agro-product Quality and Safety, Chinese Academy of Agricultural Sciences, Beijing 100081, China. Electronic address:

Animal feeding method is a crucial factor in influencing meat quality. Consumers would preferentially select meat obtained from pasture-fed animals. In this study, an untargeted metabolomic and lipidomic method based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) combined with chemometric analysis was utilized to investigate the differences between meat from free-range and intensively-fed sheep/goats. Distinct separation between these two kinds of sheep/goats meat obtained were identified by principal component analysis. Analysis of variance, fold change and orthogonal projection to latent structures discriminant analysis were then conducted to determine specific potential markers. A total of 46 potential markers were selected according to online chemical databases. The support vector machine (SVM) method was used to process the responses of the selected potential markers, and the results of metabolomics and lipidomics from an additional 59 samples revealed the discrimination rate of 89.3% and 98.3%. These findings provided a basis for differentiation of meat from sheep/goats fed in the two methods.
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http://dx.doi.org/10.1016/j.meatsci.2020.108374DOI Listing
March 2021

Identification and Validation of an Immunological Expression-Based Prognostic Signature in Breast Cancer.

Front Genet 2020 16;11:912. Epub 2020 Sep 16.

Department of Clinical Laboratory, The First Clinical Medical College of Lanzhou University, Lanzhou, China.

Emerging evidence suggests that the immune system plays a crucial role in the regulation of the response to therapy and long-term outcomes of patients with breast cancer (BRCA). In this study, we aimed to identify a significant signature based on immune-related genes to predict the prognosis of BRCA patients. The expression data were downloaded from The Cancer Genome Atlas (TCGA). The immune-related gene list, the transcription factor (TF) gene list, and the immune infiltrate scores of samples in the TCGA database were acquired from the ImmPort database, the Cistrome Cancer database, and the TIMER database, respectively. Univariate Cox regression analysis was utilized to identify prognostic immune-related differentially expressed genes (DEGs) (PIRDEGs) in BRCA. A prognostic immune signature containing 15 PIRDEGs in BRCA was established using the least absolute shrinkage and selection operator (LASSO) model with 1,000 iterations followed by a stepwise Cox proportional hazards model with a training set of 508 samples in TCGA. An independent assessment of the prognostic prediction ability of the signature was conducted using Kaplan-Meier survival analysis with a testing set of 505 samples in TCGA. We identified 466 PIRDEGs and 80 TFs among the DEGs. A gene signature containing 15 PIRDEGs was constructed. Risk scores of BRCA patients were calculated using this model, which showed a high accuracy of prognosis prediction in both the training set and testing set and could be an independent prognostic factor of BRCA patients. Our study revealed that a PIRDEG signature could be a candidate prognostic biomarker for predicting the overall survival (OS) of patients with BRCA.
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http://dx.doi.org/10.3389/fgene.2020.00912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526716PMC
September 2020

Effects of the timing of selective reduction and finishing number of fetuses on the perinatal outcome in triplets: a single-center retrospective study.

J Matern Fetal Neonatal Med 2020 Nov 15:1-6. Epub 2020 Nov 15.

Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Objective: This study aimed to evaluate the effect of the timing of selective reduction and finishing the number of fetuses on perinatal outcomes in triplets.

Method: The study assessed 417 cases of triplets. Perinatal outcomes were compared between selective reduction (SR) performed at 11-14weeks of gestation and SR performed at 15-24weeks of gestation for the same starting and finishing numbers of fetuses. Then, the perinatal outcomes of reduction to singletons and twins were compared for the same range of SR of gestational weeks.

Results: The spontaneous abortion rate was 6.5% and 14.9%, respectively, when SR was performed at 11-14weeks of gestation (214 cases) and at 15-24 weeks of gestation (94 cases) ( = .019). In total, 74 cases of triplets were reduced to singletons and 214 cases were reduced to twins when SR was performed at 11-14weeks of gestation. Preterm labor rates, low birth weight rates, birth weights, and gestational ages at delivery also showed significant differences ( < .001). In total, 35 cases of triplets were reduced to singletons and 94 cases were reduced to twins when SR was performed at 15-24weeks of gestation. The preterm labor rates, low birth weight rates, birth weights and gestational ages at delivery also significantly differed ( < .05).

Conclusions: When the starting and finishing numbers of fetuses were the same, the timing of SR could affect the spontaneous abortion rates. When the starting number of fetuses was the same, the timing of SR did not affect the neonatal outcome. However, the finishing number of fetuses was the influencing factor.
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http://dx.doi.org/10.1080/14767058.2020.1846702DOI Listing
November 2020

The bioflavonoid troxerutin prevents gestational hypertension in mice by inhibiting STAT3 signaling.

Hypertens Res 2021 Apr 30;44(4):399-406. Epub 2020 Oct 30.

Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwu Road, Jinan, 250021, Shandong, China.

Gestational hypertension is a high-risk disease for women, and the current treatments have limited efficacies. Here, we aimed to evaluate troxerutin, which is a natural monomer of flavone, in the treatment of gestational hypertension. Pregnant mice with or without pregnancy-induced hypertension (PIH) were treated with troxerutin (20 and 40 mg/kg) or vehicle. Blood pressure and proteinuria were monitored during treatment. The expression of vasodilation converting enzyme (VCE), angiotensin, TNFα, IL-6, IL-1β and IL-10 was measured by enzyme-linked immunosorbent assay (ELISA). Oxidative stress was assessed by measuring the reactive oxygen species (ROS) levels and antioxidant enzyme concentrations. Western blot analysis was used to assess the expression of p-STAT3, STAT3, SHP-1, and RNF6. Troxerutin reduced blood pressure and the expression of VCE, angiotensin, urinary protein and pro-inflammatory cytokines in a dose-dependent manner while increasing the expression of anti-inflammatory cytokines. The levels of ROS were decreased, and the levels of antioxidant enzymes were increased. Troxerutin treatment significantly suppressed STAT3/RNF6 signaling. Overexpression of RNF6 attenuated the effects of troxerutin in ameliorating inflammation and oxidative stress. Our data support the use of troxerutin for reducing gestational hypertension due to the role of troxerutin in reducing inflammation and oxidative stress.
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http://dx.doi.org/10.1038/s41440-020-00568-zDOI Listing
April 2021

Do You Feel the Same as I Do? Differences in Virtual Reality Technology Experience and Acceptance Between Elderly Adults and College Students.

Front Psychol 2020 25;11:573673. Epub 2020 Sep 25.

School of Journalism and Communication, Beijing Normal University, Beijing, China.

Virtual reality (VR) has been widely applied in medical health areas and the entertainment and tourism industries, in which elderly people are a primary target. However, most studies on VR have focused on how people respond to this new technology and its effects on younger generations. Our study explored the differences in VR experience and acceptance between elderly adults and college students. A mixed method approach including both experiments and in-depth interviews was applied in this study. Our results show that elderly adults reported a higher level of telepresence and stronger emotional responses than young adults in VR viewing regardless of the VR device. The ways in which elderly people processed and evaluated VR content and devices were different from those of young people. Elderly people reported more positive attitudes toward the video they watched than young people, but this did not necessarily lead to more positive attitudes toward the viewing experience.
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http://dx.doi.org/10.3389/fpsyg.2020.573673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546805PMC
September 2020

Macrophage-stimulating protein is decreased in severe preeclampsia and regulates the biological behavior of HTR-8/SVneo trophoblast cells.

Placenta 2021 01 6;103:33-42. Epub 2020 Oct 6.

Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) of Ministry of Education, Chengdu, Sichuan, PR China. Electronic address:

Preeclampsia (PE) is a major challenge for obstetricians. There is no effective way to block the development of PE other than terminating the pregnancy. The biological behavior of trophoblast cells, which are similar to cancer cells, may be closely related to the onset of PE. The vital role of macrophage-stimulating protein (MSP) in the development and progression of cancer has been recognized, while a role for this protein in PE has rarely been reported. This study aimed to explore whether MSP affects severe PE (sPE) and, if so, to characterize the mechanism. Patient information, blood samples and/or placental tissues were collected. An enzyme-linked immunosorbent assay (ELISA) was used to determine the plasma MSP concentration. The relationships between the plasma MSP concentration and clinical characteristics were analyzed. Immunofluorescence was performed to localize MSP in placental tissues. Western blotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to determine MSP protein and mRNA expression in placental tissues. MSP was overexpressed or underexpressed in the trophoblastic cell line HTR-8/SVneo by lentiviral transfection and the proliferation, apoptosis, migration, invasion and angiogenesis of cells were detected. MSP was downregulated in sPE, and the underexpression of MSP inhibited HTR-8/SVneo cell proliferation, migration, invasion and angiogenesis. We further verified that MSP affects the biological behavior of trophoblast cells through the β-catenin/ZEB1 signaling pathway. These results suggest that decreased MSP in the blood and placental tissues of patients with sPE, especially those with early-onset sPE, leads to reduced trophoblast cell invasion, which plays an important role in the pathogenesis of PE.
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http://dx.doi.org/10.1016/j.placenta.2020.10.004DOI Listing
January 2021

Screening and identification of biomarkers associated with the diagnosis and prognosis of lung adenocarcinoma.

J Clin Lab Anal 2020 Oct 16;34(10):e23450. Epub 2020 Jul 16.

China Medical University, Shenyang, China.

Background: In this study, we aimed to identify the pathogenesis and prognostic biomarkers of lung adenocarcinoma (LUAD).

Methods: Differentially expressed mRNAs (DEmRNAs) and single nucleotide polymorphism (SNP) mutant genes were screened. In addition, enrichment and protein-protein interaction (PPI) network analyses of the SNP-mutated genes were performed. Thereafter, the correlation between gene mutation and expression was analyzed. Finally, the mutated genes associated with LUAD prognosis were validated on the basis of The Cancer Genome Atlas (TCGA) database.

Results: A total of 2502 DEmRNAs were initially screened in this study. We identified 756 SNP-mutated genes from more than 30 cases. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the mutated genes involved in LUAD were mainly associated with the ECM-receptor interaction, focal adhesion, and calcium signaling pathways. Tumor protein p53 (TP53) and neurexin 1 (NRXN1) with the higher degree were chosen as the hub genes in the PPI network. In addition, the correlation analysis revealed six genes, including assembly factor for spindle microtubules (ASPM), centromere protein F (CENPF), contactin 3 (CNTN3), catenin delta 2 (CTNND2), PKHD1 like 1 (PKHD1L1), and semaphorin 6D (SEMA6D), and three SNP mutations at ASPM rs368020495, CENPF rs762653487, and PKHD1L1 rs768349010 sites that were found to be associated with LUAD prognosis. Further validation showed that among the aforementioned six mutated genes, CENPF was upregulated and SEMA6D was downregulated.

Conclusion: CENPF, SEMA6D, TP53, and NRXN1 were found to be closely associated with the development of LUAD.
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http://dx.doi.org/10.1002/jcla.23450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595917PMC
October 2020

The isoflavonoid calycosin inhibits inflammation and enhances beta cell function in gestational diabetes mellitus by suppressing RNF38 expression.

Immunopharmacol Immunotoxicol 2020 Aug 30;42(4):366-372. Epub 2020 Jun 30.

Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

Background: Gestational diabetes mellitus (GDM) is a medical complication and metabolic disorder associated with pregnancy. Calycosin is a traditional Chinese herbal medicine that is used for the treatment of multiple diseases. This study focused on exploring the effects and underlying mechanisms of Calycosin on GDM.

Methods: The db/+ diabetic mice model of GDM was used to evaluate the effects of calycosin administration on the symptoms of GDM mice. Blood glucose, cytokine production (interleukin 6, IL-6; tumor necrosis factor-α, TNF-α), and insulin levels were measured by ELISA assay. The expression level of signal transducer and activator of transcription 3 (STAT3), ring finger protein 38 (RNF38), and SH2-containing protein tyrosine phosphatase 1 (SHP-1) were determined by Western Blot assay. Beta cell proliferation was assessed by CCK-8 assay.

Results: Our data indicated that administration of calycosin significantly improved the GDM symptoms in pregnant db/+ mice as demonstrated by reduced blood glucose, TNF-a, and IL-6 levels as well as increased insulin level, and body weight. Furthermore, we revealed that RNF38/SHP-1/STAT3 signaling should play a critical role in calycosin-promoted beta cell function, and forced expression of RNF38 attenuated the positive effects of calycosin on beta cells.

Conclusion: Our study implied that calycosin exerts favorable effects on GDM mice rebalancing insulin sensitivity and inflammatory response.
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http://dx.doi.org/10.1080/08923973.2020.1782426DOI Listing
August 2020

Associations between gene polymorphisms and dilated cardiomyopathy in a Chinese population.

Biomark Med 2020 04 9;14(6):441-450. Epub 2020 Apr 9.

Department of Cardiology, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, China.

The present study aimed to investigate the role of gene polymorphisms in dilated cardiomyopathy (DCM) susceptibility and prognosis in a Chinese population. A total of 343 DCM patients and 451 controls were enrolled and had their blood genotyped. Survival analysis was evaluated with Kaplan-Meier curves and Cox regression analysis. G carriers (AG/GG) and AG genotype of rs237028 had a higher DCM susceptibility as well as a worse DCM prognosis. Additionally, C carriers (CT/CC) of rs652921 and G carriers (TG/GG) of rs521845 had a higher DCM risk and CC homozygote of rs652921 had a worse DCM prognosis. These associations were still significant after adjustment for the Bonferroni correction. gene polymorphisms were associated with DCM susceptibility and prognosis in the Chinese population.
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http://dx.doi.org/10.2217/bmm-2019-0384DOI Listing
April 2020

Comprehensive understanding of magnetic hyperthermia for improving antitumor therapeutic efficacy.

Theranostics 2020 19;10(8):3793-3815. Epub 2020 Feb 19.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, No. 11, First North Road, Zhongguancun, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China.

Magnetic hyperthermia (MH) has been introduced clinically as an alternative approach for the focal treatment of tumors. MH utilizes the heat generated by the magnetic nanoparticles (MNPs) when subjected to an alternating magnetic field (AMF). It has become an important topic in the nanomedical field due to their multitudes of advantages towards effective antitumor therapy such as high biosafety, deep tissue penetration, and targeted selective tumor killing. However, in order for MH to progress and to realize its paramount potential as an alternative choice for cancer treatment, tremendous challenges have to be overcome. Thus, the efficiency of MH therapy needs enhancement. In its recent 60-year of history, the field of MH has focused primarily on heating using MNPs for therapeutic applications. Increasing the thermal conversion efficiency of MNPs is the fundamental strategy for improving therapeutic efficacy. Recently, emerging experimental evidence indicates that MNPs-MH produces nano-scale heat effects without macroscopic temperature rise. A deep understanding of the effect of this localized induction heat for the destruction of subcellular/cellular structures further supports the efficacy of MH in improving therapeutic therapy. In this review, the currently available strategies for improving the antitumor therapeutic efficacy of MNPs-MH will be discussed. Firstly, the recent advancements in engineering MNP size, composition, shape, and surface to significantly improve their energy dissipation rates will be explored. Secondly, the latest studies depicting the effect of local induction heat for selectively disrupting cells/intracellular structures will be examined. Thirdly, strategies to enhance the therapeutics by combining MH therapy with chemotherapy, radiotherapy, immunotherapy, photothermal/photodynamic therapy (PDT), and gene therapy will be reviewed. Lastly, the prospect and significant challenges in MH-based antitumor therapy will be discussed. This review is to provide a comprehensive understanding of MH for improving antitumor therapeutic efficacy, which would be of utmost benefit towards guiding the users and for the future development of MNPs-MH towards successful application in medicine.
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http://dx.doi.org/10.7150/thno.40805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069093PMC
May 2021

Method for Localization Aerial Target in AC Electric Field Based on Sensor Circular Array.

Sensors (Basel) 2020 Mar 12;20(6). Epub 2020 Mar 12.

Faculty of Science, Kunming University of Science and Technology, Kunming 650504, China.

The traditional method of using electric field sensors to realize early warning of electric power safety distance cannot measure the distance of dangerous sources. Therefore, aiming at the electric field with a frequency of 50 to 60Hz (AC electric field), a new method for localization of aerial AC target by the capacitive one-dimensional spherical electric field sensor circular array is studied. This method can directly calculate the distance, elevation, and azimuth of the detector from the dangerous source. By combining the measurement principle of the spherical electric field sensor and the plane circular array theory, a mathematical model for the localization of aerial targets in an AC electric field is established. An error model was established using Gaussian noise and the effects of different layout parameters on the localization error were simulated. Based on mutual interference between sensors, minimum induced charge, and localization error, an optimal model for sensor layout was established, and it was solved by using genetic algorithms. The optimization results show that when the number of sensors is 4, the array radius is 20 cm, and the sensor radius is 1.5 cm, the ranging error is 8.4%. The detector was developed based on the layout parameters obtained from the optimization results, and the localization method was experimentally verified at 10 and 35 kV alarm distances. The experimental results show that when the detector is located at 10 kV alarm distance, the distance error is 0.18 m, the elevation error is 6.8°, and the azimuth error is 4.57°, and when it is located at 35 kV alarm distance, the distance error is 0.2 m, the elevation error is 4.8°, and the azimuth error is 5.14°, which meets the safety distance warning requirements of 10 and 35 kV voltage levels.
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http://dx.doi.org/10.3390/s20061585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146230PMC
March 2020

Relationship between polymorphisms of CXCL3 gene and preeclampsia.

J Matern Fetal Neonatal Med 2020 Jan 22:1-5. Epub 2020 Jan 22.

Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) of Ministry of Education, Chengdu, Sichuan, PR China.

Preeclampsia (PE), a pregnancy-specific disease, is a main cause of maternal and perinatal mortality in the world, the exact pathogenesis of which is still unknown. Recent studies have found it is a disorder caused by multiple factors and genes. Previously, we found a significantly abnormal expression of CXCL3 in plasma and placenta of severe preeclampsia. Here, we intend to explore the association of polymorphisms in CXCL3 gene with preeclampsia susceptibility in women from western China. Four hundred eighty-one pregnant women were involved in this case-control study, including 83 early-onset severe preeclampsia cases, 114 late-onset severe preeclampsia cases, 41 mild preeclampsia cases and 243 normal pregnancies. The rs370655 variant in CXCL3 was detected by the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). No significantly reduced risk of preeclampsia is observed in the rs370655 AA genotype compared with other genotypes (AG versus AA: OR = .82, 95%CI = .54-1.26; GG versus AA: OR = .95, 95%CI = .56-1.61). After subgroup analysis, there are still no significant differences among various genotypes in the mild preeclampsia, early-onset severe preeclampsia and late-onset sever preeclampsia. Our study suggests that rs370655 polymorphism in CXCL3 gene may be not the risk factor of preeclampsia, exploring other consequential SNPs in CXCL3 gene may help to predict the preeclampsia.
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http://dx.doi.org/10.1080/14767058.2020.1716332DOI Listing
January 2020

Saikosaponin d downregulates microRNA-155 and upregulates FGF2 to improve depression-like behaviors in rats induced by unpredictable chronic mild stress by negatively regulating NF-κB.

Brain Res Bull 2020 04 8;157:69-76. Epub 2020 Jan 8.

Traditional Chinese Medicine Research and Development Center, Guang' Anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, PR China.

Saikosaponin d (SSd) is a traditional Chinese medicine that has been widely used in depression treatment. Given the lack of studies demonstrating the underlying mechanism of action of SSd in depression, the presented study was conducted with aims of investigating the effect of SSd on rats with depression-like behaviors induced by unpredicted chronic mild stress (UCMS) and its underlying molecular mechanism. To investigate the effect of SSd on depression, rat models with depression-like behaviors were established through 3-week exposure to UCMS, followed by administration of 10 mg/kg fluoxetine, 0.75 mg/kg SSd, 1.50 mg/kg SSd, or 10 mg/kg caffeic acid phenethyl ester (CAPE). The depression-like behaviors of rats were evaluated by sucrose preference test, open field test, forced swimming test, and tail suspension test. Afterwards, the regulatory relationship among nuclear factor-κB (NF-κB), microRNA (miR)-155 and fibroblast growth factor 2 (FGF2) were detected by dual-luciferase reporter gene assay and ChIP. RT-qPCR and Western blot analysis was conducted to determine the expression of genes and proteins. Finally, hippocampal neurons were extracted from modeled rats and transfected with miR-155 mimic, miR-155 inhibitor, NF-κB overexpression plasmid, or siRNA against NF-κB. The results showed that the depression-like behaviors induced by UCMS in rats was successfully attenuated by SSd. In hippocampal neurons of rats treated with SSd, NF-κB was significantly downregulated while FGF2 was significantly upregulated. NF-κB targets miR-155 and negatively regulates the expression of FGF2. NF-κB knockdown resulted in reduced depression-like behaviors of rats. These findings provide evidence that SSd could ameliorate depression-like behaviors in the rats treated with UCMS by downregulating NF-κB and miR-155, and upregulating FGF2.
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http://dx.doi.org/10.1016/j.brainresbull.2020.01.008DOI Listing
April 2020

Analysis of five cases of hypermethioninemia diagnosed by neonatal screening.

J Pediatr Endocrinol Metab 2020 Jan;33(1):47-52

Center of Genetic Medicine, The Affiliated Obstetrics and Gynecology Hospital with Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.

Background Hypermethioninemia is a group of diseases with elevated plasma methionine (Met) caused by hereditary and non-hereditary factors, although it could also be caused by administration of the amino acid Met. Among these, the disease caused by methionine adenosyltransferase (MAT) I/III deficiency is the most common, and is characterized by persistent, isolated hypermethioninemia as well as slightly elevated homocysteine. S-adenosylmethionine is the product of Met, which can be used as a direct methyl donor of many substances, such as choline and nucleotide, and essential in the development of the body. Among the patients, most have no symptoms, and a small number have central nervous system complications with high levels of plasma Met, including mental retardation, cognitive impairment and special breathing odor. Methods In this study, five cases of MAT I/III deficiency were diagnosed and retrospectively analyzed among 220,000 newborns. Patients with high Met levels received a Met-restricted diet treatment. Results and conclusions MAT I/III deficiency is a common reason for Met elevation in neonatal screening by tandem mass spectrometry (MS/MS), which needs long-term follow-up except for these patients with explicitly benign mutations.
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http://dx.doi.org/10.1515/jpem-2019-0285DOI Listing
January 2020

Interface Nanoengineering of PdNi-S/C Nanowires by Sulfite-Induced for Enhancing Electrocatalytic Hydrogen Evolution.

ACS Appl Mater Interfaces 2020 Jan 2;12(2):2243-2251. Epub 2020 Jan 2.

Key Laboratory of Advanced Functional Materials of Nanjing , Nanjing Xiaozhuang University , Nanjing 211171 , P. R. China.

The interfacial structural design of materials in nanoscale is a promising approach to regulate the physicochemical properties of materials and further optimize material properties for a variety of potential applications. Herein, PdNi-S/C nanowires with inductive sulfite has been successfully crafted through hydrothermal synthesis and applied as a superior hydrogen evolution reaction (HER) catalyst. Based on the autocatalytic mechanism, PdNi alloy nanoparticles were synthesized by controlling reduction kinetics with the presence of formic acid. Meanwhile, the sulfite is selected as an effective inductive agent to form PdNi-S/C nanowires with amorphous interfaces. The morphology, composition, and electronic structure of the synthesized PdNi-S/C were studied in detail. The PdNi-S/C manifests excellent HER performance in alkaline solution with an overpotentials of 67 mV at current density of 10 mA cm, a Tafel slope of 69.4 mV dec, and significantly long-term durability. The improvement of HER performance of the PdNi-S/C is attributed to the one-dimensional nanowire structure, abundant sulfur vacancies and defects, and the synergistic effect between PdNi-S nanowires with the graphite carbon. Furthermore, this present work offers a novel method for structure adjustment of materials to effectively control their property and catalytic performance.
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http://dx.doi.org/10.1021/acsami.9b14598DOI Listing
January 2020

Construction of three-dimensional mesoporous carbon nitride with high surface area for efficient visible-light-driven hydrogen evolution.

J Colloid Interface Sci 2020 Mar 12;561:601-608. Epub 2019 Nov 12.

School of Chemistry and Chemical Engineering, Shandong University of Technology, Zibo 255049, PR China. Electronic address:

Carbon nitride, as an outstanding photocatalyst for hydrogen production, displays a limited photocatalytic performance on account of the insufficient light absorption and low surface area. Herein, three-dimensional mesoporous carbon nitride with large surface area was prepared by using freeze-dried cyanuric acid-melamine supramolecular aggregates and ionic liquid as precursor and template, respectively. The results find that as-prepared carbon nitride materials possess the 3D interconnected open-framework with porous channels owing to the decomposition of ionic liquid and precursor under high temperature calcination, which in favor of the contact between active sites and reactants as well as the improvement of charge carrier transport rate. Compared to the pure carbon nitride, the obtained CNF-0.005 was endowed with the ultrathin nanosheets, broaden light adsorption, high separation rate of photogenerated carriers and improved photocatalytic activity. Especially, the above-mentioned sample exhibits a superior visible light driven photocatalytic H production capability and excellent durability, as high as 129.5 μmol/h, which is about 27.6 times and 1.8 times than that of the bulk CN and pure CNF, respectively. This work opens up an ingenious strategy towards the fabrication of high-performance carbon nitride with controllable structure and improved surface area for efficient hydrogen production.
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http://dx.doi.org/10.1016/j.jcis.2019.11.035DOI Listing
March 2020

The Effects of Viewing an Uplifting 360-Degree Video on Emotional Well-Being Among Elderly Adults and College Students Under Immersive Virtual Reality and Smartphone Conditions.

Cyberpsychol Behav Soc Netw 2020 Mar 2;23(3):157-164. Epub 2019 Nov 2.

School of Journalism and Communication, Beijing Normal University, Beijing, People's Republic of China.

Positive emotions are important for the physical and mental health of elderly adults. Previous research has suggested that the emotion processing mechanisms of elderly adults differ from those of young people. The current study used a mixed-methods approach to explore the emotional impacts of viewing an uplifting 360° videos under immersive (using a virtual reality [VR] headset) and nonimmersive (using a smartphone) conditions on elderly populations and young people. In Study 1, we conducted a pre-post treatment between-subject field experiment (smartphone vs. VR) among 58 seniors (aged 60 years and above) in a community center in Beijing, China. One-on-one semistructured interviews of each participant were conducted after the experiment. In Study 2, we conducted a between-subject laboratory experiment with the same design among college students. The results show that while both VR and smartphone viewing conditions led to a significant positive effect on the self-reported emotions of the college students, only the smartphone viewing condition had a significant impact on the emotional well-being of the elderly participants. For college students, immersive VR had a stronger effect on inducing positive emotions than smartphone, but for elderly people, the smartphone viewing condition was more effective in improving emotional wellbeing than immersive VR. An analysis of the qualitative data from interviewing the elderly participants also revealed a divergence in the acceptance of VR technologies among elderly adults, and the sense of telepresence had both positive and negative effects on the elderly participants' emotions and experiences.
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http://dx.doi.org/10.1089/cyber.2019.0273DOI Listing
March 2020

[Analysis of AGR1 gene variants in an infant with early-onset argininemia].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2019 Oct;36(10):996-998

Genetic Medicine Center, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University (Nanjing Maternal and Child Health Hospital), Nanjing, Jiangsu 210004, China.

Objective: To explore the genetic basis for an infant with early-onset argininemia.

Methods: Potential variant was detected with an Ion Torrent semiconductor sequencer using a gene panel for inherited diseases. Suspected variants were verified by Sanger sequencing.

Results: Genetic testing indicated that he has carried c.560+2T>C and c.811T>C compound heterozygous variant of the AGR1 gene, which were inherited from his father and mother, respectively. Among these, c.560+2T>C was suspected to be pathogenic, while c.811T>C was of unknown clinical significance, and both were not reported previously.

Conclusion: The c.560+2T>C and c.811T>C compound heterozygous variants of the AGR1 gene probably underlies the argininemia in this child. Above finding has enriched the variant spectrum of the AGR1 gene.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2019.10.011DOI Listing
October 2019

miR-212-5p attenuates ferroptotic neuronal death after traumatic brain injury by targeting Ptgs2.

Mol Brain 2019 09 18;12(1):78. Epub 2019 Sep 18.

Department of Forensic Genetics, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.

Ferroptosis, a newly discovered form of iron-dependent regulated cell death, has been implicated in traumatic brain injury (TBI). MiR-212-5p has previously been reported to be downregulated in extracellular vesicles following TBI. To investigate whether miR-212-5p is involved in the ferroptotic neuronal death in TBI mice, we first examined the accumulation of malondialdehyde (MDA) and ferrous ion, and the expression of ferroptosis-related molecules at 6 h, 12 h, 24 h, 48 h and 72 h following controlled cortical impact (CCI) in mice. There was a significant upregulation in the expression of Gpx4 and Acsl4 at 6 h, Slc7a11 from 12 h to 72 h, and Nox2 and Sat1 from 6 h to 72 h post injury. Similarly, an upregulation in the expression of Gpx4 at 6 h, Nox2 from 6 h to 72 h, xCT from 12 h to 72 h, and Sat1 at 72 h after CCI was observed at the protein level. Interestingly, MDA and ferrous ion were increased whereas miR-212-5p was decreased in the CCI group compared to the sham group. Furthermore, we found that overexpression of miR-212-5p attenuated ferroptosis while downregulation of miR-212-5p promoted ferroptotic cell death partially by targeting prostaglandin-endoperoxide synthase-2 (Ptgs2) in HT-22 and Neuro-2a cell lines. In addition, administration of miR-212-5p in CCI mice significantly improved learning and spatial memory. Collectively, these findings indicate that miR-212-5p may protect against ferroptotic neuronal death in CCI mice partially by targeting Ptgs2.
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http://dx.doi.org/10.1186/s13041-019-0501-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749650PMC
September 2019