Publications by authors named "Yuting Xie"

41 Publications

Single Dose of SHR-1222, a Sclerostin Monoclonal Antibody, in Healthy Men and Postmenopausal Women With Low Bone Mass: A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation, Phase I Study.

Front Pharmacol 2021 20;12:770073. Epub 2021 Oct 20.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

SHR-1222 is a humanized monoclonal antibody targeting sclerostin and has the potential to promote bone formation and reduce bone resorption. This study was aimed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of SHR-1222 in healthy men and postmenopausal women with low bone mass (BMD). It was a randomized, double-blind, placebo-controlled, dose-escalation, phase I study. Subjects received SHR-1222 at 50, 100, 200, 300, and 400 mg sequentially or matching placebo subcutaneously. Totally, 50 subjects with low BMD were enrolled and randomly assigned; 10 received placebo and 40 received SHR-1222 (50 mg, n = 4; 100, 200, 300, or 400 mg, n = 9). The most common adverse events that occurred at least 10% higher in subjects with SHR-1222 treatment than those with placebo were decreased blood calcium, blood urine present, increased blood cholesterol, electrocardiogram T wave abnormal, urinary tract infection, increased blood pressure diastolic, and positive bacterial test. All the above adverse events were mild in severity and well resolved except one of increased blood cholesterol in a subject lost to follow-up. The serum SHR-1222 concentration increased in a dose-dependent manner. Administration of SHR-1222 upregulated the bone-formation markers N-terminal propeptide of type 1 procollagen, osteocalcin, and bone-specific alkaline phosphatase, while downregulated the bone-resorption marker β-C-telopeptide. The BMD at the lumbar spine notably rose after a single dose of SHR-1222. The largest increase occurred in the 400 mg cohort (3.8, 6.7, and 6.1% on day 29, 57, and 85, respectively; compared with 1.4, 0.8, and 1.0% in the placebo group). Although 10.0% of subjects receiving SHR-1222 tested positive for anti-SHR-1222 antibodies, no obvious effects of antibody formation were found on pharmacokinetics. Overall, SHR-1222 was well tolerated at doses from 50 to 400 mg and is a promising new remedy for osteoporosis. http://www.clinicaltrials.gov, NCT03870100.
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http://dx.doi.org/10.3389/fphar.2021.770073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564351PMC
October 2021

Liver Fibrosis: Therapeutic Targets and Advances in Drug Therapy.

Front Cell Dev Biol 2021 21;9:730176. Epub 2021 Sep 21.

Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, Department of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Liver fibrosis is an abnormal wound repair response caused by a variety of chronic liver injuries, which is characterized by over-deposition of diffuse extracellular matrix (ECM) and anomalous hyperplasia of connective tissue, and it may further develop into liver cirrhosis, liver failure or liver cancer. To date, chronic liver diseases accompanied with liver fibrosis have caused significant morbidity and mortality in the world with increasing tendency. Although early liver fibrosis has been reported to be reversible, the detailed mechanism of reversing liver fibrosis is still unclear and there is lack of an effective treatment for liver fibrosis. Thus, it is still a top priority for the research and development of anti-fibrosis drugs. In recent years, many strategies have emerged as crucial means to inhibit the occurrence and development of liver fibrosis including anti-inflammation and liver protection, inhibition of hepatic stellate cells (HSCs) activation and proliferation, reduction of ECM overproduction and acceleration of ECM degradation. Moreover, gene therapy has been proved to be a promising anti-fibrosis method. Here, we provide an overview of the relevant targets and drugs under development. We aim to classify and summarize their potential roles in treatment of liver fibrosis, and discuss the challenges and development of anti-fibrosis drugs.
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http://dx.doi.org/10.3389/fcell.2021.730176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490799PMC
September 2021

RNA-seq analyses of Marine Medaka (Oryzias melastigma) reveals salinity responsive transcriptomes in the gills and livers.

Aquat Toxicol 2021 Nov 16;240:105970. Epub 2021 Sep 16.

College of the Environment and Ecology, Xiamen University, Xiamen 361102, China. Electronic address:

Increasing salinity levels in marine and estuarine ecosystems greatly influence developmental, physiological and molecular activities of inhabiting fauna. Marine medaka (Oryzias melastigma), a euryhaline research model, has extraordinary abilities to survive in a wide range of aquatic salinity. To elucidate how marine medaka copes with salinity differences, the responses of Oryzias melastigma after being transferred to different salt concentrations [0 practical salinity units (psu), 15 psu, 30 psu (control), 45 psu] were studied at developmental, histochemical and transcriptome levels in the gill and liver tissues. A greater number of gills differentially expressed genes (DEG) under 0 psu (609) than 15 psu (157) and 45 psu (312), indicating transcriptomic adjustments in gills were more sensitive to the extreme hypotonic environment. A greater number of livers DEGs were observed in 45 psu (1,664) than 0 psu (87) and L15 psu (512), suggesting that liver was more susceptible to hypertonic environment. Further functional analyses of DEGs showed that gills have a more immediate response, mainly in adjusting ion balance, immune and signal transduction. In contrast, DEGs in livers were involved in protein synthesis and processing. We also identified common DEGs in both gill and liver and found they were mostly involved in osmotic regulation of amino sugar and nucleotide sugar metabolism and steroid biosynthesis. Additionally, salinity stresses showed no significant effects on most developmental and histochemical parameters except increased heartbeat with increasing salinity and decreased glycogen after transferred from stable conditions (30 psu) to other salinity environments. These findings suggested that salinity-stress induced changes in gene expressions could reduce the effects on developmental and histochemical parameters. Overall, this study provides a useful resource for understanding the molecular mechanisms of fish responses to salinity stresses.
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http://dx.doi.org/10.1016/j.aquatox.2021.105970DOI Listing
November 2021

Epigenetic regulation in fibrosis progress.

Pharmacol Res 2021 11 22;173:105910. Epub 2021 Sep 22.

Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Department of Gastroenterology and Hepatology, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address:

Fibrosis, a common process of chronic inflammatory diseases, is defined as a repair response disorder when organs undergo continuous damage, ultimately leading to scar formation and functional failure. Around the world, fibrotic diseases cause high mortality, unfortunately, with limited treatment means in clinical practice. With the development and application of deep sequencing technology, comprehensively exploring the epigenetic mechanism in fibrosis has been allowed. Extensive remodeling of epigenetics controlling various cells phenotype and molecular mechanisms involved in fibrogenesis was subsequently verified. In this review, we summarize the regulatory mechanisms of DNA methylation, histone modification, noncoding RNAs (ncRNAs) and N6-methyladenosine (m6A) modification in organ fibrosis, focusing on heart, liver, lung and kidney. Additionally, we emphasize the diversity of epigenetics in the cellular and molecular mechanisms related to fibrosis. Finally, the potential and prospect of targeted therapy for fibrosis based on epigenetic is discussed.
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http://dx.doi.org/10.1016/j.phrs.2021.105910DOI Listing
November 2021

Sustained Attention Deficits in Adults With Juvenile-Onset Type 1 Diabetes Mellitus.

Psychosom Med 2021 10;83(8):906-912

From the Medical Psychological Center (Zou, Y. Liu, J. Zhu, C. Li, Du, X. Zhu), The Second Xiangya Hospital, Central South University; Medical Psychological Institute of Central South University (X. Zhu); National Clinical Research Center for Mental Disorders (X. Zhu), The Second Xiangya Hospital; Department of Psychology (He) and Hunan Key Laboratory of Children's Psychological Development and Brain Cognitive Science (He), Hunan First Normal University; National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology (Zou, Y. Liu, Xie, Zhou, X. Li), The Second Xiangya Hospital of Central South University; Xiangya School of Nursing (F. Liu), Central South University, Hunan Province; and Department of Nutrition (Huang), The Second Xiangya Hospital, Central South University, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan Province, China.

Objective: This study aimed to investigate whether patients with juvenile-onset type 1 diabetes mellitus (T1DM) have poorer sustained attention than their counterparts with adult-onset T1DM, and whether there is a relationship between diabetes-related variables and sustained attention.

Methods: This study included 76 participants with juvenile-onset T1DM, 68 participants with adult-onset T1DM, and 85 healthy controls (HCs). All participants completed the Sustained Attention to Response Task, Beck Depression Inventory-II, and the Chinese version of the Wechsler Adult Intelligence Scale.

Results: The juvenile-onset group showed more omission errors (p = .007) than the adult-onset group and shorter reaction time (p = .005) than HCs, whereas the adult-onset group showed no significant differences compared with HCs. Hierarchical linear regression analysis revealed that the age of onset was associated with omission errors in T1DM participants (β = -0.275, t = -2.002, p = .047). In the juvenile-onset group, the omission error rate were associated with the history of severe hypoglycemia (β = 0.225, t = 1.996, p = .050), whereas reaction time was associated with the age of onset (β = -0.251, t = -2.271, p = .026). Fasting blood glucose levels were significantly associated with reaction time in both the juvenile-onset and adult-onset groups (β = -0.236, t = -2.117, p = .038, and β = 0.259, t = 2.041, p = .046, respectively).

Conclusions: Adults with juvenile-onset T1DM have sustained attention deficits in contrast to their adult-onset counterparts, suggesting that the disease adversely affects the developing brain. Both the history of severe hypoglycemia and fasting blood glucose levels are factors associated with sustained attention impairment. Early diagnosis and treatment in juvenile patients are required to prevent the detrimental effects of diabetes.
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http://dx.doi.org/10.1097/PSY.0000000000000992DOI Listing
October 2021

Residual β-cell function after 10 years of autoimmune type 1 diabetes: prevalence, possible determinants, and implications for metabolism.

Ann Transl Med 2021 Apr;9(8):650

National Clinical Research Center for Metabolic Disease, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

Background: Type 1 diabetes (T1D) has long been considered a progressive autoimmune disease resulting in the failure of pancreatic β-cell function and absolute endogenous insulin deficiency. However, several studies have demonstrated patients with T1D have detectable C-peptide levels long after diagnosis, which has remarkable clinical significance. Since this issue has not been systematically explored in non-Caucasian populations, we aimed to identify the prevalence of residual β-cell function and its related clinical features in Chinese long-term T1D patients.

Methods: We enrolled 109 patients with T1D for ≥10 years and administered a mixed-meal tolerance test (MMTT). Fasting and postprandial C-peptide (FCP/PCP) levels were measured to evaluate the insulin secretion function of β-cells. Patients whose FCP and PCP levels were both below the lower detection limit (16.7 pmol/L) were grouped as 'β-cell function depleted', while others were thought to have 'residual β-cell function'. Demographic data, metabolic status, and diabetic complications were compared between patients with or without residual β-cell function.

Results: 38.5% of subjects retained residual β-cell function, and among those, 33.3% responded to MMTT by a two-fold or greater rise of their FCP levels. Clinical features associated with residual β-cell function were older age of diagnosis [27.5 (interquartile range:11.5-37.0) 17.0 (interquartile range: 8.0-30.0) years, P=0.037], lower HbA1c (64.6±20.3 72.4±18.5 mmol/mol, P=0.026), and reduced rate of hypoglycemia (23.8% 52.2%, P=0.003). Age of diagnosis was positively correlated with detectable FCP level (r=0.393, P=0.020). Individuals diagnosed after 30 years of age tended to retain residual β-cell function (OR =3.016, P=0.044). We found no association between residual β-cell function and chronic diabetic complications.

Conclusions: Residual β-cell function can be found in nearly 40% of long-term patients with T1D in China and is associated with older age at diagnosis and better glucose control. The relationship between residual β-cell function and chronic diabetic complications remains to be explored.
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http://dx.doi.org/10.21037/atm-20-7471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106063PMC
April 2021

Poor guideline adherence in type 1 diabetes education in real-world clinical practice: Evidence from a multicentre, national survey.

Patient Educ Couns 2021 11 17;104(11):2740-2747. Epub 2021 Apr 17.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. Electronic address:

Objective: To examine how physicians implement guidelines to deliver insulin dosing education for type 1 diabetes patients in real-world settings.

Methods: A nationally representative sample of endocrinologists from top tertiary hospitals in China was obtained by a multistage random sampling method (n = 385). Knowledge, perceptions and practices of insulin dosing were assessed by validated questionnaires. Multivariable logistic regression was used to identify independent determinants of clinical practice and knowledge.

Results: Only 20.5% of endocrinologists correctly answered> 75% of the items regarding insulin dosing knowledge. Only 37.7% of endocrinologists reported often teaching insulin-to-carbohydrate ratio and insulin sensitivity factor. Practice behaviours were independently associated with guideline familiarity (OR: 5.92, 95% CI: 3.36-10.41), receiving standardized training (OR: 2.00, 95% CI:1.23-3.25), self-reported lack of time (OR: 0.58, 95% CI:0.34-0.99) and insufficient teaching approaches (OR: 0.57, 95% CI:0.33-0.97) CONCLUSIONS: There was a large gap between guidelines and clinical practice in insulin dosing education. Modifiable factors, including self-reported lack of time, unfamiliarity with guidelines, the shortage of medical training and educational tools hinder insulin dosing education.

Practice Implications: Sufficient medical training and educational tools are important to optimize insulin dosing education. The current care paradigm should also be modified to relieve the burden of physicians.
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http://dx.doi.org/10.1016/j.pec.2021.04.010DOI Listing
November 2021

Three-phasic pattern of C-peptide decline in type 1 diabetes patients with partial remission.

Diabetes Metab Res Rev 2021 Nov 7;37(8):e3461. Epub 2021 May 7.

Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.

Aims: To explore the different patterns of C-peptide decline in patients with and without partial remission of newly diagnosed type 1 diabetes (T1D).

Materials And Methods: A total of 298 patients with new-onset T1D were followed up regularly at 3 months' interval to investigate the loss of C-peptide. Partial remission was determined by postprandial C-peptide ≥300 pmol/L or insulin dose-adjusted A1c ≤ 9 in the absence of C-peptide. Beta-cell function was defined as preserved, residual or failed by postprandial C-peptide of ≥200 pmol/L, 50-200 pmol/L or ≤50 pmol/L, respectively.

Results: Altogether, 199 out of 298 patients (125 adults) had partial remission. The pattern of C-peptide change in patients with partial remission was three-phasic, demonstrating an upward trend followed by a downward trend of fast first and then slow, while the pattern in patients without partial remission was biphasic, showing an initial fast fall and a subsequent slower decrease. The patterns remained consistent when patients were stratified by the age of onset. At 3 years, there were 71% of the patients with partial remission still had preserved or residual beta-cell function, while 89% of the patients who had no partial remission developed beta-cell function failure. In patients whose partial remission ended, the average C-peptide was still higher than duration-matched patients without partial remission.

Conclusions: Patients with partial remission of T1D have a distinct three-phasic pattern of C-peptide decline, other than the widely recognized biphasic pattern. The effect of partial remission still exist​s after remission ends.
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http://dx.doi.org/10.1002/dmrr.3461DOI Listing
November 2021

Structural, dielectric, magnetic and optical properties of double perovskite oxide SmNiMnOnanoparticles synthesized by a sol-gel process.

Nanotechnology 2021 Apr 22;32(28). Epub 2021 Apr 22.

National Laboratory of Solid State Microstructures, School of Physics, Nanjing University, Nanjing 210093, People's Republic of China.

Here we report on the structural, dielectric, magnetic and optical properties of double perovskite SmNiMnO(SNMO) nanoparticles synthesized by a sol-gel method. Structural Reitveld refinements on x-ray powder diffraction data revealed that the SNMO nanoparticles crystallized in a monoclinic crystal structure with2/space group. SEM and (HR)TEM images revealed the phase purity and single-crystalline nature of the SNMO nanoparticles. XPS spectra confirmed the presence of Sm, Niand Mnions in the SNMO nanoparticles and oxygen in the forms of lattice oxygen and the hydroxyls species. SNMO ceramics exhibited relaxor-type dielectric behavior, well fitted by modified Curie-Weiss law. Such dielectric behavior originated from the interactions of random dipoles arisen from the B-site cations disorder accompanied with the variations in local electric fields and local strain fields due to the different radii of B-site cations, and/or the virtual electrons hopping between the Niand Mncations. Magnetic data demonstrate the variations of the magnetic transitions at low temperatures and the spin glass-like behavior below 11 K, which is attributed to the spin fluctuations induced by the competing interactions between the ferromagnetic (FM) and antiferromagnetic phases. Large positive Curie-Weiss temperature () indicates the dominant FM super-exchange interactions in the SNMO samples. The SNMO nanoparticles have a direct optical band gap of 1.42 eV, close to 1.34 eV in a single junction solar cell. That enables the SNMO nanoparticles to be useful for solar cell absorbers.
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http://dx.doi.org/10.1088/1361-6528/abf59fDOI Listing
April 2021

Understanding the sodium ion transport properties, deintercalation mechanism, and phase evolution of a NaMnSiO cathode by atomistic simulation.

Phys Chem Chem Phys 2021 Jan;23(2):1750-1758

The State Key Laboratory base of Novel Functional Materials and Preparation science, The Faculty of Materials Science and Chemical Engineering, Ningbo Univ., Ningbo, 315211, P. R. China.

Molecular dynamics (MD) together with the first principles method (DFT) reveal that Na+ is capable of migrating three dimensionally in a Na2Mn2Si2O7 cathode material. Migration along the a-axis and c-axis have the same mechanism, that is, alternating between the Na1 and Na2 route with a similar local environment and distance. Long-distance hopping between two Na2 atoms or between Na1 and Na2 atoms is crucial for continuous migration along the b-axis. Also, the anti-site phenomenon is identified, and it facilitates the migration of the Na ions. Four intermediate phases are determined according to the formation energy curve and, as a result, the voltage profile is predicted accurately. The state of charge (SOC) dependency of the Na+ energy shows that the mobility of Na+ is highly inhibited in the fully discharged state. Upon the deintercalation of sodium ions, Na+ is activated immediately. A maximal DNa+ value of 3.6 × 10-9 cm2 s-1 and a low energy barrier of ca. 0.26 eV at the deintercalation level of x = 0.25 are observed. Because of the scarcity of Na+, DNa+ experiences a sharp decrease at the end of deintercalation. Despite the low level of Na+ mobility in the range of 0.25 < x < 1, Na2Mn2Si2O7 is still a potential cathode material for use in sodium ion batteries (SIBs).
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http://dx.doi.org/10.1039/d0cp06529cDOI Listing
January 2021

An automated structured education intervention based on a smartphone app in Chinese patients with type 1 diabetes: a protocol for a single-blinded randomized controlled trial.

Trials 2020 Nov 23;21(1):944. Epub 2020 Nov 23.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.

Background: Although evidence had demonstrated the effectiveness of smartphone apps in diabetes care, the majority of apps had been developed for type 2 diabetes mellitus (T2DM) patients and targeted at populations outside of China. The effects of applying a smartphone app with structured education on glycemic control in type 1 diabetes mellitus (T1DM) are unclear. A digital, culturally tailored structured education program was developed in a smartphone app (Yi tang yun qiao) to provide an automated, individualized education program aimed at improving self-management skills in patients with T1DM in China. This trial aims to investigate the effectiveness of this smartphone app among Chinese T1DM patients.

Methods And Analysis: This single-blinded, 24-week, parallel-group randomized controlled trial of a smartphone app versus routine care will be conducted in Changsha, China. We plan to recruit 138 patients with T1DM who will be randomly allocated into the intervention group (automated, individualized education through an app) or routine care group. The intervention will last for 24 weeks. The primary outcome will be the change in glycated hemoglobin (HbA1c) from baseline to week 24. The secondary outcomes will include time in range, fasting blood glucose, levels of serum triglycerides and cholesterol, blood pressure, body mass index, quality of life, diabetes self-care activities, diabetes self-efficacy, depression, anxiety, and patient satisfaction. Adverse events will be formally documented. Data analysis will be conducted using the intention-to-treat principle with appropriate univariate and multivariate methods. Missing data will be imputed with a multiple imputation method under the "missing at random" assumption.

Discussion: This trial will investigate the effectiveness of an app-based automated structured education intervention for Chinese patients with T1DM. If the intervention is effective, this study will provide a strategy that satisfies the need for effective lifelong diabetes care to reduce the disease burden and related complications resulting from T1DM.

Trial Registration: ClinicalTrials.gov NCT04016987 . Registered on 29 October 2019.
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http://dx.doi.org/10.1186/s13063-020-04835-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681998PMC
November 2020

Effects of Yinzhihuang Granules on Serum Liver Enzymes in Jaundice Patients: A Real-World Study Based on HIS Data.

Evid Based Complement Alternat Med 2020 5;2020:3843752. Epub 2020 Nov 5.

School of Statistics, Renmin University of China, Beijing 100872, China.

Objective: Our aim was to analyze the influence of Yinzhihuang granules on serum liver enzymes in jaundice patients and to provide real-world evidence for the efficacy evaluation of Yinzhihuang granules in treating jaundice.

Methods: We constructed a data warehouse which integrates real-world electronic medical records from the hospital information system of multiple 3A hospitals in China and used a descriptive statistical method to analyze the changes in the serum liver enzymes of the jaundice patients treated with Yinzhihuang granules and then used Wilcoxon signed-rank to test the changes in the indicators caused by the treatment.

Results: After being treated with Yinzhihuang granules, the jaundice patients had a decrease in the average serum levels of total bilirubin, indirect bilirubin, aspartate aminotransferase, glutamyl transpeptidase, and alkaline phosphatase, and the differences were statistically significant ( < 0.05) but had no significant changes in the average serum levels of direct bilirubin and alanine aminotransferase ( > 0.05).

Conclusion: The data analysis on the real-world electronic medical records demonstrate that Yinzhihuang granules help to reduce jaundice patients' serum levels of total bilirubin, indirect bilirubin, aspartate aminotransferase, glutamyl transpeptidase, and alkaline phosphatase, but there is no evidence that Yinzhihuang granules help to reduce the jaundice patients' serum levels of direct bilirubin and alanine aminotransferase.
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http://dx.doi.org/10.1155/2020/3843752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661130PMC
November 2020

N‑linoleyltyrosine protects PC12 cells against oxidative damage via autophagy: Possible involvement of CB1 receptor regulation.

Int J Mol Med 2020 Nov 24;46(5):1827-1837. Epub 2020 Aug 24.

Department of Pharmacy, Development and Regeneration Key Laboratory of Sichuan Province, Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China.

Oxidative stress is one of the main pathogenic factors of neurodegenerative diseases. As the ligand of cannabinoid type 1 (CB1) and 2 (CB2) receptors, anandamide (AEA) exerts benign antioxidant activities. However, the instability of AEA results in low levels in vivo, which limit its further application. Based on the structure of AEA, N‑linoleyltyrosine (NITyr) was synthesized in our laboratory and was hypothesized to possess a similar function to that of AEA. To the best of our knowledge, the present study demonstrates for the first time, the activities and mechanisms of NITyr. NITyr treatment attenuated hydrogen peroxide (H2O2)‑induced cytotoxicity, with the most promiment effect observed at 1 µmol/l. Treatment with NITyr also suppressed the H2O2‑induced elevation of reactive oxygen species (ROS) and enhanced the expression of the autophagy‑related proteins, LC3‑II, beclin‑1, ATG 5 and ATG13. The autophagic inhibitor, 3‑methyladenine, reversed the effects of NITyr on ROS levels and cellular viability. Furthermore, AM251, a CB1 receptor antagonist, but not AM630 (a CB2 receptor antagonist), diminished the effects of NITyr on cell viability, ROS generation and autophagy‑related protein expression. However, NITyr increased the protein expression of both the CB1 and CB2 receptors. Therefore, NITyr was concluded to protect PC12 cells against H2O2‑induced oxidative injury by inducing autophagy, a process which may involve the CB1 receptor.
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http://dx.doi.org/10.3892/ijmm.2020.4706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521587PMC
November 2020

Status of social avoidance and distress in emerging adults with Type 1 diabetes mellitus and its association with self-management and glycemic control.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2020 Jul;45(7):834-839

Teaching and Research Section of Clinical Nursing, Second Xiangya Hospital, Central South University, Changsha 410011, China.

: Emerging adult patients with Type 1 diabetes mellitus (T1DM) appear to have a reduced opportunities on learning and exercise, a decreased skill in learning and work, a lower degree of social support due to fear and avoidance of social interaction. This study aimed to assess the level of social avoidance and distress in emerging adults with T1DM, and to explore the correlation between social avoidance and distress and self-management or glycemic control. : A total of 342 T1DM patients aged 18-30 years old were recruited from 8 tertiary hospitals in Hunan Province from September 2014 to February 2019. The questionnaire included general information questionnaire, the Social Avoidance and Distress Scale (SAD), and Self-management Scale of Type 1 Diabetes for Chinese Adults (SMOD-CA). The total scores of SAD in emerging adult patients with T1DM were compared with those of norm. Correlation between glycated hemoglobin (HbA1c) and social avoidance and distress of emerging adult patients with T1DM was analyzed. : The total score of SAD (11.13±6.18) in emerging adults with T1DM was significantly higher than that in healthy adults (=77.06, <0.01). Pearson correlation analysis showed that the scores of SAD, social avoidance subscale, and social distress subscale were negatively correlated with the scores of SMOD-CA (all <0.01), and they were positively correlated with HbA1c (all <0.01). Multivariate linear regression analysis showed that social avoidance and distress, self-management, gender, and educational level were independent influential factors for HbA1c in emerging adults with T1DM. : The degree of social avoidance and distress of emerging adult patients with T1DM is higher than that of healthy people. The higher the degree of social avoidance and distress, the lower the level of self-management and the worse the control of blood sugar. Attention should be paid to social avoidance and distress in emerging adults with T1DM, and targeted interventions should be formulated.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2020.190415DOI Listing
July 2020

The protective effect of astaxanthin on the ganglion cell complex in glutamate/aspartate transporter deficient mice, a model of normal tension glaucoma, analyzed by spectral domain-optical coherence tomography.

Biochem Biophys Rep 2020 Sep 29;23:100777. Epub 2020 Jun 29.

Department of Ophthalmology, Hirosaki University Graduate School of Medicine, Hirosaki, 036-8562, Japan.

Astaxanthin (AST), a natural marine carotenoid, possess a wide variety of biological functions. In particular, as a strong antioxidant, AST effectively scavenges oxygen free radicals and reduces oxidative stress. In addition, recent studies have suggested that AST attenuates glutamate-induced apoptosis and cytotoxicity. The glutamate/aspartate transporter (GLAST) deficient (GLAST) mouse is a mouse model of normal tension glaucoma (NTG) caused by both the glutamate neurotoxicity and oxidative stress in the retina. In the present study, we investigated the effects of AST on the ganglion cell complex, indicator of glaucomatous structural damage, using spectral domain-optical coherence tomography. As a result, AST significantly attenuated the thinning of ganglion cell complex in GLAST mice in comparison to an AST-free control group. Our results suggest the possibility that AST has protective effects against glutamate neurotoxicity and oxidative stress in the retina. At present, the only treatment for NTG that is available in the clinical setting is to reduce the IOP as much as possible. Thus, our results suggest that AST supplementation may be effective for some types of NTG in which glutamate neurotoxicity and oxidative stress are involved.
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http://dx.doi.org/10.1016/j.bbrep.2020.100777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330488PMC
September 2020

Structure-Based Optimization of 10-DEBC Derivatives as Potent and Selective Pim-1 Kinase Inhibitors.

J Chem Inf Model 2020 06 29;60(6):3287-3294. Epub 2020 May 29.

National Institute of Biological Sciences, Beijing, Beijing 102206, China.

Pim-1 kinase has been widely regarded as an attractive target for anticancer drugs. Here, we reported our continued efforts in structure-based optimization of compound 10-DEBC, a previously identified micromolar Pim-1 inhibitor. Guided by the Site Identification by Ligand Competitive Saturation (SILCS) method, we quickly obtained a series of 10-DEBC derivatives with significantly improved activity and selectivity. In particular, compound exhibited an IC value of 0.9 nM, as well as 220- and 8-fold selectivity over Pim-2 and Pim-3 kinases, respectively.
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http://dx.doi.org/10.1021/acs.jcim.0c00245DOI Listing
June 2020

Effects of Diabetic Ketoacidosis on Executive Function in Children With Type 1 Diabetes: Evidence From Wisconsin Card Sorting Test Performance.

Psychosom Med 2020 05;82(4):359-365

From the Medical Psychological Center, The Second Xiangya Hospital (J. He, J. Zhu, Du, Sh. Li, Si. Li, X. Zhu), Central South University, Changsha, China; Department of Psychology (J. He), The First Normal University, Changsha, China; Hunan Key Laboratory of Children's Psychological Development and Brain Cognitive Science (J. He), Changsha, China; Medical Psychological Institute of Central South University (J. Zhu, Du, Sh. Li, Si. Li, X. Zhu), Changsha, China; National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital (X. Zhu), Changsha, China; Department of Metabolism and Endocrinology, The Second Xiangya Hospital (Xie, X. Li, Zhou), Central South University, Changsha, China; National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital (Xie, X. Li, Zhou), Changsha, China; and Children's Healthcare Institution, Hu Nan Children's Hospital (W. He), The University of South China Academy of Pediatrics, Changsha, China.

Objective: Diabetic ketoacidosis (DKA) in patients with type 1 diabetes mellitus (T1DM) is known to affect memory function, but little is known about its impact on executive function. This study aimed to determine whether a history of DKA was associated with changes in executive function in children with T1DM.

Methods: The sample consisted of 99 patients with T1DM with histories of DKA, 82 patients with T1DM without DKA, and 100 healthy controls aged 7 to 18 years. Neuropsychological function and emotion assessments were performed in all participants. The Wisconsin Card Sorting Test (WCST) was used to assess executive function.

Results: Compared with healthy controls, the DKA group (but not the non-DKA group) had a significantly lower mean intelligence quotient (IQ; p = .006, Cohen d = 0.528) and a significantly higher rate of WCST perseverative errors (p = .006, Cohen d = 0.475). In the DKA group, the age at DKA onset was significantly associated with the IQ (p = .001) and the number of completed WCST categories (p = .046). Higher hemoglobin A1c levels were associated significantly with lower IQ (p < .001), increased rate of WCST perseverative errors (p = .015), and completion of fewer WCST categories (p = .027).

Conclusions: DKA has implications for executive function in children with T1DM. These findings emphasize the importance of DKA prevention in patients with known T1DM, especially younger children with newly diagnosed T1DM.
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http://dx.doi.org/10.1097/PSY.0000000000000797DOI Listing
May 2020

Decline Pattern of Beta-cell Function in Adult-onset Latent Autoimmune Diabetes: an 8-year Prospective Study.

J Clin Endocrinol Metab 2020 07;105(7)

Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Objective: To explore the decline pattern and possible determinants of beta-cell function progression in patients with latent-onset autoimmune diabetes in adults (LADA).

Research Design And Methods: In this 8-year prospective study, 106 LADA individuals underwent annual follow-up and their pattern of beta-cell function progression was assessed. Beta-cell function failure was defined by fasting C-peptide (FCP) < 75 pmol/L. Other clinical characteristics, including age of onset, body mass index (BMI), and glutamic acid decarboxylase autoantibody (GADA) titer, were analyzed to find out possible determinants of beta-cell function progression.

Results: The dropout rate was 4.7%. During the 8-year follow-up period, 29 (28.7%) of the 101 subjects developed beta-cell function failure. The decline pattern of C-peptide in LADA was biphasic, showing an initial rapid linear progression and then followed by a stable mode. The declination speed of FCP was 55.19 pmol/L/year (95% CI, -62.54 to -47.84, P < 0.001) during the first 5 years and 4.62 pmol/L/year (95% CI, -69.83 to 60.60, P = 0.790) thereafter. Further analysis showed that GADA titer was the most valuable discriminatory parameter related to a higher risk of development of beta-cell function failure (GADA titer of 173.5 WHO units/mL; area under the curve [AUC], 0.824). Beta-cell function failure occurred in 71.3% of high-GADA titer patients while only 6.2% of low-titer patients.

Conclusions: The decline pattern of C-peptide was a fast-followed-by-slow biphasic mode, with about a quarter of LADA patients developing beta-cell function failure during the first 8 years. GADA titer less than 173.5 WHO units /mL was propitious for the preservation of beta-cell function.
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http://dx.doi.org/10.1210/clinem/dgaa205DOI Listing
July 2020

A spectral-domain optical coherence tomographic analysis of Rdh5-/- mice retina.

PLoS One 2020 9;15(4):e0231220. Epub 2020 Apr 9.

Department of Ophthalmology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.

Purpose: To investigate the longitudinal findings of spectral-domain optical coherence tomography (SD-OCT) in relation to the morphologic features in Rdh5 knockout (Rdh5-/-) mice.

Materials And Methods: The mouse retina was segmented into four layers; the inner retinal (A), outer plexiform and outer nuclear (B), rod/cone (C), and retinal pigment epithelium (RPE)/choroid (D) layers. The thickness of each retinal layer of Rdh5-/- mice was longitudinally and quantitatively measured at six time points from postnatal months (PM) 1 to PM6 using SD-OCT. Age-matched C57BL/6J mice were employed as wild-type controls. The data were statistically compared using Student's t-test. The fundus appearance was assessed, histologic and ultrastructural examinations were performed in both groups.

Results: Layers A and B were significantly thinner in the Rdh5-/- mice than in the wild-type C57BL/6J mice during the observation periods. Layers C and D became thinner in the Rdh5-/- mice than in the wild-type mice after PM6. Although no abnormalities corresponding to whitish fundus dots were detected by SD-OCT or histologic examinations, the intracellular accumulation of low-density vacuoles was noted in the RPE of the Rdh5-/- mice by electron microscopy. The photoreceptor nuclei appeared less dense in the Rdh5-/- mice than in the wild-type mice.

Discussion: The results from the present study suggest that although it is difficult to detect qualitative abnormalities, SD-OCT can detect quantitative changes in photoreceptors even in the early stage of retinal degeneration induced by the Rdh5 gene mutation in mice.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231220PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144952PMC
July 2020

Frequency, clinical characteristics, and determinants of partial remission in type 1 diabetes: Different patterns in children and adults.

J Diabetes 2020 Oct 20;12(10):761-768. Epub 2020 Apr 20.

Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, China.

Background: Partial remission (PR) is a special stage in type 1 diabetes (T1D). The different patterns of PR frequency, characteristics, and determinants in juvenile and adult patients are unclear, and data on Chinese are lacking.

Methods: A total of 186 children and 114 adults with T1D who were regularly followed up in a cohort were included for analysis. PR was defined according to C-peptide ≥300 pmol/L or index of insulin dose-adjusted hemoglobin A1c ≤9, as previously recommended. C-peptide and islet autoantibodies were determined with chemiluminescence and radioimmunoassay, respectively.

Results: The frequency of PR in children was higher than that in adults, with the proportion being 69.9% and 58.8%, respectively (P < .05). For juvenile-onset T1D, the frequency of PR gradually decreased as the onset age decreased, from 87.5% in 13- to 18-year olds to 46.5% in under 6-year olds. Multivariable analyses showed that onset age and male sex were positively related with the frequency of PR in children, while the related factors in adults were initial glycosylated hemoglobin A1c and C-peptide levels. The median PR duration was similar in children (14.8 ± 1.2 months) and adults (16.4 ± 1.9 months). Older onset age was related with a longer PR duration in children, but no such associations were found in adult individuals.

Conclusions: Children and adults with T1D have different patterns on PR frequency, clinical characteristics, and determinants. For patients during this special phase, the relatively high C-peptide level and to reduce insulin dosage accordingly should be emphasized in clinical practice.
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http://dx.doi.org/10.1111/1753-0407.13044DOI Listing
October 2020

PD-1 and PD-L1 Expression in Peripheral CD4/CD8+ T Cells Is Restored in the Partial Remission Phase in Type 1 Diabetes.

J Clin Endocrinol Metab 2020 06;105(6)

Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Context: Partial remission (PR) in type 1 diabetes (T1D) is accompanied by downregulation of the immune response. Programmed cell death-1 (PD-1) and its ligand (PD-L1) are important immunosuppressive molecules, but their changes in the PR phase are unclear.

Objective: We investigated the dynamic changes of PD-1/PD-L1 expression on T cells around the PR phase in T1D.

Methods: Ninety-eight T1D patients were recruited cross-sectionally and grouped according to PR status into nonremitters (individuals who did not undergo PR during the disease course; n = 39), pre-PR (n = 15), mid-PR (n = 30), and post-PR (n = 14) subgroups. PR was defined according to C-peptide level ≥300 pmol/L or index of insulin-adjusted hemoglobin A1c ≤9 as recommended. Among all the 98 patients, 29 newly diagnosed individuals were prospectively followed up for 1 year. The dynamic changes of PD-1/PD-L1 expression, frequency of regulatory T cells (Tregs) and IL-35+ Tregs among peripheral CD4/CD8+ T cells were determined.

Results: PD-1/PD-L1 on CD4+/CD8+ T cells showed a dynamic change around the PR phase: lowest in pre-PR phase, restored in mid-PR phase, and declined again in post-PR phase. Conversely, this pattern did not occur for nonremitters. Notably, PD-1 expression on CD8+ T cells in mid-PR was positively correlated with the length of the PR phase. The percentages of circulating Tregs and IL-35+ Tregs showed no relation to PR.

Conclusions: The PR phase is associated with restoration of PD-1/PD-L1 on CD4+ and CD8+ T cells, suggesting that PD-1/PD-L1 may be a potential target for prolonging this phase in T1D.
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http://dx.doi.org/10.1210/clinem/dgaa130DOI Listing
June 2020

Different Effects of Structured Education on Glycemic Control and Psychological Outcomes in Adolescent and Adult Patients with Type 1 Diabetes: A Systematic Review and Meta-Analysis.

Int J Endocrinol 2020 26;2020:9796019. Epub 2020 Feb 26.

Xiangya School of Nursing, Central South University, Changsha, Hunan Province, China.

Aim: This systematic review aimed at investigating the effectiveness of structured education (SE) in improving glycemic control and psychological outcomes in adolescent and adult patients with type 1 diabetes.

Methods: Electronic databases (EMBASE, Medline, PubMed, and the Cochrane Library) and the reference lists of included studies were searched from the beginning of the database through April 2019. Randomized controlled trials comparing SE with a control condition and reporting a change in glycosylated hemoglobin (HbA1c) level were included. The primary outcome was glycemic control measured by HbA1c. Secondary outcomes were diabetes-related distress, well-being, depression, and quality of life.

Results: Eighteen studies representing 2759 patients were included. Twelve studies targeted adolescents and six targeted adults. Adolescent patients who were randomized to the intervention group did not show significant improvement of HbA1c in the short (SMD = -0.04; 95% CI: -0.14 to 0.06; =0.41), medium (SMD = -0.03; 95% CI: -0.13 to 0.07; =0.41), medium (SMD = -0.03; 95% CI: -0.13 to 0.07; =0.41), medium (SMD = -0.03; 95% CI: -0.13 to 0.07; =0.41), medium (SMD = -0.03; 95% CI: -0.13 to 0.07; =0.41), medium (SMD = -0.03; 95% CI: -0.13 to 0.07.

Conclusions: Development of more efficient SE programs according to the patients' personal characteristics is needed.
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http://dx.doi.org/10.1155/2020/9796019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061135PMC
February 2020

Establishment of a type 1 diabetes structured education programme suitable for Chinese patients: type 1 diabetes education in lifestyle and self adjustment (TELSA).

BMC Endocr Disord 2020 Mar 10;20(1):37. Epub 2020 Mar 10.

Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, China.

Background: Various guidelines recommend that all adults diagnosed with type 1 diabetes (T1D) should be offered an evidence based, structured education programme (SEP) to optimize self-management care. China has a 13,000 annual increase in newly diagnosed T1D cases, of which 65% are adults. However, there is yet no validated SEP targeted to T1D patients in China. The purpose of this study is to establish a structured T1D self-management education programme-'Type 1 Diabetes Education in Lifestyle and Self Adjustment' (TELSA) that is adapted to medical and cultural practices in China.

Methods: TELSA programme was developed based on the ADDIE model, following three steps: i) Semi-structured interviews were administered to 10 healthcare professionals (HCPs) and 13 T1D patients. Different topic guides, focusing on 4 dimensions including goals, contents, format of delivery, and quality assurance, were designed for either HCPs or patients. The interviews were recorded and analysed with thematic analysis. ii) Extracted themes were modified according to Delphi consultation. iii) Preliminary courses were conducted as pilot study to evaluate the effects of TELSA and optimization of the curriculum was finalized accordingly.

Results: A total of 18 themes in 4 dimensions of the programme design were identified in the final version: i) goals: 'behaviour modification' and 'outcome improvement'; ii) contents: 'living with T1D', 'self-monitoring of blood glucose', 'knowing insulin', 'insulin dose adjustment', 'carbohydrates and carbohydrate counting', 'hypoglycaemia', 'complications of diabetes', 'managing psychological issues', 'physical activity', and 'question-and-answer'; iii) format: 'multidisciplinary team combined with peer support', 'face-to-face education followed by remote learning', and '2-day programme held on weekends'; and iv) quality assurance: 'after-class quiz', 'patients' feedback', and 'long-term evaluation on effectiveness'.

Conclusions: A type 1 diabetes structured education programme in China was set up and shown to be applicable under local medical, social, and cultural environment.

Trial Registration: NCT03610984. Date of registration: August 2, 2018.
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http://dx.doi.org/10.1186/s12902-020-0514-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063731PMC
March 2020

Complicated curve association of body weight at diagnosis with C-peptide in children and adults with new-onset type 1 diabetes.

Diabetes Metab Res Rev 2020 05 20;36(4):e3285. Epub 2020 Jan 20.

Institute of Metabolism and Endocrinology, The Second Xiangya Hospital and the Diabetes Center, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China.

Aim: To investigate the association of body mass index (BMI) or BMI z-score (BMIz) at diagnosis with β-cell function in new-onset type 1 diabetes (T1D) patients in children and adults.

Methods: This was a retrospective cohort study; 256 children (<18 years) and 245 adults (≥18 years) with less than 1-year duration were recruited and followed for 4 years with an interval of 12 months. Smooth curve fitting, a two-piecewise linear model, and Cox proportional hazards models were utilized to investigate the influence of BMI/BMIz on C-peptide levels.

Results: Heavier patients (BMIz ≥ -1 in children and BMI in adults ≥20.2 kg/m ) had greater C-peptide with a complicated J curve in all age groups after adjustment for age of onset, sex, and disease duration. Moreover, after 4 years of follow-up, patients with higher BMI/BMIz had a lower risk of β-cell failure (HR = 0.7; 95% CI, 0.6-1.0; P = .026). However, no association was found between baseline BMI/BMIz at diagnosis and C-peptide rate of decline during 1 year follow-up.

Conclusion: Association between BMI/BMIz and C-peptide in T1D followed a complicated J curve pattern, and heavier patients had greater C-peptide at diagnosis and a lower risk of β-cell failure at 4 years, suggesting that baseline BMI is a useful predictor for β-cell function in patients with T1D.
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http://dx.doi.org/10.1002/dmrr.3285DOI Listing
May 2020

Excess Glutamate May Cause Dilation of Retinal Blood Vessels in Glutamate/Aspartate Transporter-Deficient Mice.

Biomed Res Int 2019 11;2019:6512195. Epub 2019 Nov 11.

Department of Ophthalmology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.

Purpose: To investigate the longitudinal findings of fundus features and spectral-domain optical coherence tomography (SD-OCT) to characterize the morphologic features in a mouse model of defective glutamate/aspartate transporter (GLAST mice).

Materials And Methods: The fundus findings and SD-OCT images were longitudinally recorded at five time points from postnatal (P) 22 to P156 in GLAST mice. As a control wild type, age-matched C57BL/6J mice were employed. The mouse retina was subdivided into five layers, and the thickness of each layer was longitudinally measured by InSight® using SD-OCT pictures. The SD-OCT findings were compared with the histologic appearances. The diameter of the retinal blood vessels was measured by the ImageJ® software program using SD-OCT images. The data were statistically compared between both age-matched mouse groups.

Results: The retinal blood vessels appeared more dilated in GLAST mice than in wild-type mice. This tendency was statistically significant at all time points after P44 by analyses using SD-OCT images. The ganglion cell complex (GCC) and outer nuclear layer (ONL) were significantly thinner in GLAST mice at all time points after P80 than in the wild-type mice. This tendency was more clearly indicated by SD-OCT than histologic sections.

Discussion: In the present study, we found for the first time the dilation of the retinal blood vessels and the thinning of the ONL in GLAST mice, in addition to the thinning of the GCC.
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http://dx.doi.org/10.1155/2019/6512195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881573PMC
April 2020

Discovery of Novel Pim-1 Kinase Inhibitors with a Flexible-Receptor Docking Protocol.

J Chem Inf Model 2019 10 17;59(10):4116-4119. Epub 2019 Oct 17.

National Institute of Biological Sciences , No. 7 Science Park Road, Zhongguancun Life Science Park , Beijing 102206 , China.

A flexible-receptor docking protocol was designed for treating binding-site side-chain flexibility by integrating essential aspects of "Conformational Selection" and "Induced Fit" in a hierarchical fashion. Assessed in a diverse set of pharmaceutically relevant targets, this protocol showed improved performance in reproducing binding poses and ligand enrichment studies compared to rigid-receptor docking. Moreover, it has also exhibited encouraging efficiency in prospective ligand discovery for Pim-1 kinase, which led to novel Pim-1 inhibitors with single-digit nanomolar potencies.
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http://dx.doi.org/10.1021/acs.jcim.9b00494DOI Listing
October 2019

Factors Influencing Patients' Intentions to Use Diabetes Management Apps Based on an Extended Unified Theory of Acceptance and Use of Technology Model: Web-Based Survey.

J Med Internet Res 2019 08 13;21(8):e15023. Epub 2019 Aug 13.

Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, China.

Background: Diabetes poses heavy social and economic burdens worldwide. Diabetes management apps show great potential for diabetes self-management. However, the adoption of diabetes management apps by diabetes patients is poor. The factors influencing patients' intention to use these apps are unclear. Understanding the patients' behavioral intention is necessary to support the development and promotion of diabetes app use.

Objective: This study aimed to identify the determinants of patients' intention to use diabetes management apps based on an integrated theoretical model.

Methods: The hypotheses of our research model were developed based on an extended Unified Theory of Acceptance and Use of Technology (UTAUT). From April 20 to May 20, 2019, adult patients with diabetes across China, who were familiar with diabetes management apps, were surveyed using the Web-based survey tool Sojump. Structural equation modeling was used to analyze the data.

Results: A total of 746 participants who met the inclusion criteria completed the survey. The fitness indices suggested that the collected data fit well with the research model. The model explained 62.6% of the variance in performance expectancy and 57.1% of the variance in behavioral intention. Performance expectancy and social influence had the strongest total effects on behavioral intention (β=0.482; P=.001). Performance expectancy (β=0.482; P=.001), social influence (β=0.223; P=.003), facilitating conditions (β=0.17; P=.006), perceived disease threat (β=0.073; P=.005), and perceived privacy risk (β=-0.073; P=.012) had direct effects on behavioral intention. Additionally, social influence, effort expectancy, and facilitating conditions had indirect effects on behavioral intention that were mediated by performance expectancy. Social influence had the highest indirect effects among the three constructs (β=0.259; P=.001).

Conclusions: Performance expectancy and social influence are the most important determinants of the intention to use diabetes management apps. Health care technology companies should improve the usefulness of apps and carry out research to provide clinical evidence for the apps' effectiveness, which will benefit the promotion of these apps. Facilitating conditions and perceived privacy risk also have an impact on behavioral intention. Therefore, it is necessary to improve facilitating conditions and provide solid privacy protection. Our study supports the use of UTAUT in explaining patients' intention to use diabetes management apps. Context-related determinants should also be taken into consideration.
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http://dx.doi.org/10.2196/15023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711042PMC
August 2019

Evaluation of Ficus tikoua leaves extract as an eco-friendly corrosion inhibitor for carbon steel in HCl media.

Bioelectrochemistry 2019 Aug 9;128:49-55. Epub 2019 Mar 9.

School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400044, China.

An effective and biodegradable Ficus tikoua leaves extract was studied as a corrosion inhibitor for carbon steel in hydrochloric acid. Systematic electrochemical experiments and morphological characterization were carried out to investigate the properties of the corrosion inhibitor. Meanwhile, quantum chemical calculations were performed to aid further understanding of the electrochemical mechanism. The electrochemical results reveal that the extract inhibitors act as a mixed-type with an inhibition efficiency up to 95.8% at 298 K. Moreover, this extract shows good inhibory activity at a wide range of temperatures and the corresponding results were further confirmed by morphological analysis. The chemical formulae of these major components are fully optimized in the DFT with B3LYP in the gas phase and the base set is 6-311++G (d, p).
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http://dx.doi.org/10.1016/j.bioelechem.2019.03.001DOI Listing
August 2019

Use, Perspectives, and Attitudes Regarding Diabetes Management Mobile Apps Among Diabetes Patients and Diabetologists in China: National Web-Based Survey.

JMIR Mhealth Uhealth 2019 02 8;7(2):e12658. Epub 2019 Feb 8.

Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, China.

Background: The diabetes disease burden in China is heavy, and mobile apps have a great potential for diabetes management. However, there is a lack of investigation of diabetes app use among Chinese diabetes patients and diabetologists. The perspectives and attitudes of diabetes patients and diabetologists regarding diabetes apps are also unclear.

Objective: Our objectives were to investigate diabetes patients' and diabetologists' use, attitudes, and perspectives, as well as patients' needs, with respect to diabetes apps to provide information regarding the optimal design of diabetes apps and the best strategies to promote their use.

Methods: Diabetes patients and diabetologists across China were surveyed on the WeChat (Tencent Corp) network using Sojump (Changsha ran Xing InfoTech Ltd) from January 23, 2018, to July 30, 2018. In total, 2 survey links were initially sent to doctors from 46 Latent Autoimmune Diabetes of Adults Study collaborative hospitals in China in 25 major cities and were spread on their WeChat contacts network. We also published the patient survey link on 3 WeChat public accounts and requested diabetes patients to fill out questionnaires. A multivariate regression analysis was used to identify associations of demographic and basic disease information with app usage among adult patients.

Results: Overall, 1276 individuals from 30 provincial regions responded to the patient survey; among them, the overall app awareness rate was 29.94% (382/1276) and usage was 15.44% (197/1276). The usage was higher among patients with type 1 diabetes (T1DM) than among patients with type 2 diabetes (T2DM; 108/473, 22.8% vs 79/733, 10.8%; P<.001). The multivariate regression analysis showed that diabetes type, age, education, family income, and location were associated with app use in adult patients (P<.05). The need for and selection of diabetes apps differed slightly between patients with T1DM and patients with T2DM. The reasons why patients discontinued the use of an app included limited time (59/197, 29.9%), complicated operations (50/197, 25.4%), ineffectiveness for glycemic control (48/197, 24.4%), and cost (38/197, 19.3%). Of the 608 responders to the diabetologist survey, 40.5% (246/608) recommended diabetes apps to patients and 25.2% (153/608) used diabetes apps to manage patients. The greatest obstacles to the diabetologists' use of apps to manage diabetes patients include limited time (280/608, 46.1%), legal issues (129/608, 21.2%), patients' distrust (108/608, 17.8%), and billing issues (66/608, 10.9%).

Conclusions: The awareness and use of diabetes apps in Chinese people with diabetes and the proportion of diabetologists using diabetes apps to manage patients are low. Designing apps targeting different patient needs and conducting high-quality randomized controlled trials will improve the effectiveness of the apps, provide evidence for patients to choose suitable apps, and be conducive to the promotion of app use.
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http://dx.doi.org/10.2196/12658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384538PMC
February 2019

The findings of optical coherence tomography of retinal degeneration in relation to the morphological and electroretinographic features in RPE65-/- mice.

PLoS One 2019 29;14(1):e0210439. Epub 2019 Jan 29.

Department of Ophthalmology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.

Purpose: Mutations of the gene encoding RPE65 cause Leber congenital amaurosis (LCA) retinitis pigmentosa (RP). The optical coherence tomography (OCT) is increasingly utilized to noninvasively evaluate various types of retinal diseases, including RP. The present study was conducted to characterize the OCT findings of the RPE65-/- mice-an animal model of LCA and RP-in relation to the morphological features based on histological and electron microscopic findings as well as electroretinography (ERG) features.

Materials And Methods: RPE65-/- mice were employed as a model of retinal degeneration. C57BL/6J mice were used as a wild-type control. OCT was performed on the RPE65-/- mice from postnatal day (P) 22 to 170. The longitudinal changes in the OCT images and fundus pictures were analyzed both qualitatively and quantitatively in comparison to those of C57BL/6J mice. The OCT images were also compared to the histological and electron microscopic findings. Full field combined rod and cone ERG was performed to analyze the relationship between morphology based on OCT and the amplitudes of the a- and b-waves.

Results: In the RPE65-/- mice, the photoreceptor rod and cone layer appeared as a diffuse hyperreflective zone contiguous with the inner segment ellipsoid zone (IS-EZ) on OCT, even on P22, whereas the IS-EZ and interdigitation zone were clearly identified in the age-matched C57BL/6J mice. The histological analyses revealed that the regular arrangement of the photoreceptor inner and outer segments was gradually lost in the RPE65-/- mice. On electron microscopy, most of the rod outer segments were degenerated from P21 to P35, whereas outer segments became variably shorter after P49 although ultrastructure appeared to normalize. The thickness of the outer nuclear layer of RPE65-/- mice was slowly and progressively reduced in comparison to C57BL/6J mice. Although the thickness of the inner and outer segment layer of RPE65-/- mice was significantly decreased in comparison to C57BL/6J mice, the change was not progressive, at least until P170. Even at P35, the amplitudes of both a- and b-waves on ERG were severely deteriorated in comparison to those of C57BL/6J mice. Mottled depigmented spots appeared throughout the fundus in RPE65-/- mice after P72, and were detected as hyperreflective deposits under the retinal pigment epithelium on OCT.

Discussion: The pathological changes in the inner and outer segments layer of RPE65-/- mice were identified as diffuse hyperreflective changes on OCT. The rod outer segments showed degeneration in the early postnatal periods but became morphologically normalized in the disc structure after P49, although the sizes of the length of the rod outer segments were variable. OCT could not qualitatively differentiate the early degeneration of rods from the late variability in size of rods. Although the morphology of the photoreceptor outer segments was relatively preserved in the RPE65-/- mice, the amplitudes of ERG were severely disturbed. These structural and functional deficits may be derived from the defective supply of 11-cis-retinol to the photoreceptors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210439PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350961PMC
October 2019
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