Publications by authors named "Yi Lu"

1,977 Publications

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Evaluation of nutrition status of very preterm infants in neonatal intensive care units using different growth indicators.

Nutr Clin Pract 2021 Aug 2. Epub 2021 Aug 2.

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

Background:  Nutrition status of very preterm infants in the neonatal intensive care unit (NICU) is strongly associated with postnatal growth. This study aimed to develop indicators of nutrition status using growth data of very preterm infants during hospitalization.

Methods: The data of 596 newborns from eight NICUs were retrospectively analyzed. Inclusion criteria were birth at <32 weeks' gestation, NICU admission ≤24 h after delivery, and length of hospital stay ≥28 days. Three indicators were evaluated: (indicator I) prevalence of extrauterine growth restriction (EUGR); (indicator II) z-score for change in weight from birth to discharge, adjusted for birth weight z-score and gestational age; and (indicator III) change in weight z-score from birth to discharge, adjusted for birth weight z-score, gestational age, and time to regain birth weight. Using data from NICU 1 as the reference for the latter two indicators, we established linear regression models of the adjusted change in weight z-score from birth to discharge. The difference between the observed value and the baseline value (calculated by the two models) served as the nutrition indices.

Results: The prevalence of EUGR differed significantly between the eight NICUs (P = .009). Statistically significant differences were found between the mean indices calculated by the other two models (all P < .05).

Conclusions: Indicator III, change in weight z-score from birth to discharge (adjusted for birth weight z-score, gestational age, and time to regain birth weight), appears to be the most accurate for evaluating the quality of nutrition in the NICU.
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http://dx.doi.org/10.1002/ncp.10741DOI Listing
August 2021

Three-dimensional Navigation-guided, Prone, Single-position, Lateral Lumbar Interbody Fusion Technique.

J Vis Exp 2021 Jul 15(173). Epub 2021 Jul 15.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School;

Lateral interbody fusion provides a significant biomechanical advantage over the traditional transforaminal lumbar interbody fusion due to the large implant size and optimal implant position. However, current methods for lateral interbody cage placement require either a two-staged procedure or a single lateral decubitus position that precludes surgeons from having either full access to the posterior spine for direct decompression or comfortable pedicle screw placement. Herein is one institution's experience with 10 cases of a prone single-position approach for simultaneous access to the anterior and posterior lumbar spine. This allows both lateral lumbar interbody cage placement, direct posterior decompression, and pedicle screw placement, all in one position. Three-dimensional (3D) navigation is utilized for increased precision in both approaching the lateral spine and interbody cage placement. The traditional blind psoas muscle tubular dilation was also modified. Tubular retractors and lateral vertebral body retractor pins were used to minimize the risks to the lumbar plexus.
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http://dx.doi.org/10.3791/62662DOI Listing
July 2021

RNA-seq and Experiments Reveal the Protective Effect of Curcumin against 5-Fluorouracil-Induced Intestinal Mucositis via IL-6/STAT3 Signaling Pathway.

J Immunol Res 2021 21;2021:8286189. Epub 2021 Jul 21.

Department of Integrated Traditional Chinese and Western Medicine, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang Province 310022, China.

Although first-line chemotherapy drugs, including 5-fluorouracil (5-FU), remain one of the major choice for cancer treatment, the clinical use is also accompanied with dose-depending toxicities, such as intestinal mucositis (IM), in cancer patients undergoing treatment. IM-induced gastrointestinal adverse reactions become frequent reason to postpone chemotherapy and have negative impacts on therapeutic outcomes and prognosis. Various studies have evidenced the anticancer role of curcumin in many cancers; except for this effect, studies also indicated a protective role of curcumin in intestinal diseases. Therefore, in this study, we investigated the effect of curcumin on inflammation, intestinal epithelial cell damage in an IM model. 5-FU was used to induce the model of IM in intestinal epithelial cells, and curcumin at different concentrations was administrated. The results showed that curcumin efficiently attenuated 5-FU-induced damage to IEC-6 cells, inhibited the levels of inflammatory cytokines, attenuated the 5-FU-induced inhibition on cell viability, and displayed antiapoptosis effect on IEC-6 cells. Further RNA-sequencing analysis and experiment validation found that curcumin displays its protective effect against 5-FU-induced IM in intestinal epithelial cells by the inhibition of IL-6/STAT3 signaling pathway. Taken together, these findings suggested that curcumin may be provided as a therapeutic agent in prevention and treatment of chemotherapy-induced IM.
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http://dx.doi.org/10.1155/2021/8286189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318760PMC
July 2021

Pharmacodynamic effects of indobufen compared with aspirin in patients with coronary atherosclerosis.

Eur J Clin Pharmacol 2021 Jul 31. Epub 2021 Jul 31.

Departments of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Purpose: This study aimed to investigate the pharmacodynamic effects of indobufen and low-dose aspirin in patients with coronary atherosclerosis.

Methods: In the first phase, 218 patients with coronary atherosclerosis were randomly assigned to receive aspirin 100 mg once daily (standard dose); 100 mg once every 2 days; 100 mg once every 3 days; 50 mg twice daily; 75 mg once daily; 50 mg once daily; or indobufen 100 mg twice daily for 1 month. In the second phase, 20 healthy subjects were treated with indobufen 100 mg twice daily for 1 week followed after a 2-week washout by aspirin 100 mg once daily for 1 week. The primary outcome was arachidonic acid-induced platelet aggregation (PL), and the secondary outcomes included plasma thromboxane B (TXB) and urinary 11-dehydro-TXB (11-dh-TXB) levels at the end of each treatment.  RESULTS: In the first phase, compared with aspirin 100 mg once daily: all aspirin groups had similar suppression of PL whereas indobufen group had significantly less suppressed PL. Aspirin given every second or third day, and indobufen produced less suppression of plasma TXB. All treatment regimens produced similar inhibition of 11-dh-TXB. In the second phase, compared with aspirin, indobufen produced less suppression of plasma TXB at 8 h and 12 h after the last dose.

Conclusions: Aspirin 50 mg twice daily, 75 mg once daily, and aspirin 50 mg once daily produce antiplatelet effects that are similar to aspirin 100 mg once daily. Aspirin given less often than once daily and indobufen 100 mg twice daily do not suppress platelets as effectively as aspirin 100 mg once daily.
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http://dx.doi.org/10.1007/s00228-021-03177-yDOI Listing
July 2021

Genetic association study of childhood aggression across raters, instruments, and age.

Transl Psychiatry 2021 07 30;11(1):413. Epub 2021 Jul 30.

Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGG) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGG. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E-06), PCDH7 (P = 2.0E-06), and IPO13 (P = 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (r) among rater-specific assessment of AGG ranged from r = 0.46 between self- and teacher-assessment to r = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range [Formula: see text]: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r = ~-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range [Formula: see text]: 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
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http://dx.doi.org/10.1038/s41398-021-01480-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324785PMC
July 2021

Letter to the Editor - Increased risk of ischemic heart disease in patients with bipolar disorder: A population-based study.

J Affect Disord 2021 Jul 23;294:481-482. Epub 2021 Jul 23.

The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China; Department of Clinical Medicine, Nanshan School, Guangzhou Medical University, Guangzhou, 511436, China.

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http://dx.doi.org/10.1016/j.jad.2021.07.074DOI Listing
July 2021

USP24-GSDMB complex promotes bladder cancer proliferation via activation of the STAT3 pathway.

Int J Biol Sci 2021 11;17(10):2417-2429. Epub 2021 Jun 11.

Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.

Bladder cancer is the fourth and tenth most common malignancy in men and women worldwide, respectively. One of the main reasons for the unsatisfactory therapeutic control of bladder cancer is that the molecular biological mechanism of bladder cancer is complex. Gasdermin B (GSDMB) is one member of the gasdermin family and participates in the regulation of cell pyroptosis. The role of GSDMB in bladder cancer has not been studied to date. TCGA database was used to exam the clinical relevance of GSDMB. Functional assays such as MTT assay, Celigo fluorescent cell-counting assay, Annexin V-APC assay and xenografts were used to evaluate the biological role of GSDMB in bladder cancer. Mass spectrometry and immunoprecipitation were used to detect the protein interaction between GSDMB and STAT3, or GSDMB and USP24. Western blot and immunohistochemistry were used to study the relationship between USP24, GSDMB and STAT3. In this study, bioinformatics analysis indicated that the mRNA expression level of GSDMB in bladder cancer tissues was higher than that in adjacent normal tissues. Then, we showed that GSDMB promoted bladder cancer progression. Furthermore, we demonstrated that GSDMB interacted with STAT3 to increase the phosphorylation of STAT3 and modulate the glucose metabolism and promote tumor growth in bladder cancer cells. Besides, we also showed that USP24 stabilized GSDMB to activate STAT3 signaling, which was blocked by the USP24 inhibitor. We suggested that aberrantly up-regulated GSDMB was responsible for enhancing the growth and invasion ability of bladder cancer cells. Then, we showed that GSDMB could bind to STAT3 and activate STAT3 signaling in bladder cancer. Furthermore, we also demonstrated that USP24 interacted with GSDMB and prevented GSDMB from degradation in bladder cancer cells. Therefore, the USP24/GSDMB/STAT3 axis may be a new targetable signaling pathway for bladder cancer treatment.
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http://dx.doi.org/10.7150/ijbs.54442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315027PMC
June 2021

LncRNA-Malat1 promoting inflammatory response aggravates cerebral ischemia-reperfusion neuronal injury in rats by targeting miR-211-5p.

Biochem Pharmacol 2021 Jul 26:114694. Epub 2021 Jul 26.

Key Laboratory of Biochemistry and Molecular Pharmacology, Department of Pharmacology, Chongqing Medical University, Chongqing 400016, China. Electronic address:

Background: Ischemic stroke is one kind of disorder of cerebral blood circulation, which poses a severe threaten to human health and quality of life, causing serious economic loss to families and society. LncRNA-Malat1(Metastasis-associated lung adenocarcinoma transcript 1) and miRNA-211-5p are abnormally expressed in stroke patients and in the middle cerebral ischemia-reperfusion injury (CIRI) model. However, the involvement between LncRNA-Malat1 and miR-211-5p in cerebral ischemia-reperfusion neuronal injury and its mechanism remain unclear.

Methods: The middle cerebral ischemia-reperfusion injury (CIRI) model was established in rat, and the rat primary neuron injury model induced by oxygen-glucose deprivation/reoxygenation (OGD/R) was simulated in vitro. Level of LncRNA-Malat1, miR-211-5p and COX-2 mRNA were detected via RT-qPCR. The protein levels of COX-2, BAX and BCL-2 were measured by western blot. MTT assay was performed to detect cell viability.

Results: In our study, LncRNA-Malat1 and COX-2 were up-regulated while miR-211-5p down-regulated in vitro and in vivo. Knockdown of LncRNA-Malat1 improved neurological deficit scores, reduced cerebral infarction volume in vivo, and significantly promoted cell viability, reduced apoptosis and proinflammatory factors PGE2 and IL-10 in vitro. More importantly, the level of miR-211-5p was negatively correlated with that of LncRNA-Malat1 and COX-2. Knockdown of LncRNA-Malat1 inhibited the expression of COX-2 by up-regulating miR-211-5p.

Conclusion: Higher expression of LncRNA-Malat1 was involved in neuronal injury, LncRNA-Malat1 knockdown may reduce inflammation and apoptosis by modulating miR-211-5p, which provided a new therapeutic strategy for clinical stroke intervention targets.
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http://dx.doi.org/10.1016/j.bcp.2021.114694DOI Listing
July 2021

RRM2 Regulates Sensitivity to Sunitinib and PD-1 Blockade in Renal Cancer by Stabilizing ANXA1 and Activating the AKT Pathway.

Adv Sci (Weinh) 2021 Jul 28:e2100881. Epub 2021 Jul 28.

Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.

Renal cell carcinoma (RCC) is a malignant tumor of the kidneys. Approximately 70% of RCC cases are clear cell renal cell carcinoma with von Hippel-Lindau (VHL) gene mutation and activation of the vascular endothelial growth factor (VEGF) pathway. Tyrosine kinase inhibitors (TKIs) targeting VEGF have emerged as promising agents for RCC treatment. Apart from primary resistance, acquired resistance to TKIs after initial tumor regression is common in RCC. Recently, immune checkpoint inhibition, including PD-1/PD-L1 blockade, alone or in combination with TKIs has improved the overall survival of patients with RCC. Ribonucleotide reductase subunit M2 (RRM2) has been reported in many types of cancer and has been implicated in tumor progression. However, the role of RRM2 in TKIs resistance in RCC remains unclear. In this study, the authors have demonstrated that RRM2 is upregulated in sunitinib-resistant RCC cells and patient tissues. They also find that RRM2 stabilizes ANXA1 and activates the AKT pathway independent of its ribonucleotide reductase activity, promoting sunitinib resistance in RCC. Moreover, RRM2 regulated antitumor immune responses, and knockdown of RRM2 enhance the anti-tumor efficiency of PD-1 blockade in renal cancer. Collectively, these results suggest that aberrantly expressed RRM2 may be a promising therapeutic target for RCC.
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http://dx.doi.org/10.1002/advs.202100881DOI Listing
July 2021

DNAzyme Sensor Uses Chemiluminescence Resonance Energy Transfer for Rapid, Portable, and Ratiometric Detection of Metal Ions.

Anal Chem 2021 Jul 26. Epub 2021 Jul 26.

Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.

DNAzymes have emerged as an important class of sensors for a wide variety of metal ions, with florescence DNAzyme sensors as the most widely used in different sensing and imaging applications because of their fast response time, high signal intensity, and high sensitivity. However, the requirements of an external excitation light source and its associated power increase the cost and size of the fluorometer, making it difficult to be used for portable detections. To overcome these limitations, we report herein a DNAzyme sensor that relies on chemiluminescence resonance energy transfer (CRET) without the need for external light. The sensor is constructed by combining the functional motifs from both Pb-dependent 8-17 DNAzyme conjugated to fluorescein (FAM) and hemin/G-quadruplex that mimics horseradish peroxidase to catalyze the oxidation of luminol by HO to yield chemiluminescence. In the absence of Pb, the hybridization between the enzyme and substrate strands bring the FAM and hemin/G-quadruplex in close proximity, resulting in CRET. The presence of Pb ions can drive the cleavage on the substrate strand, resulting in a sharp decrease in the melting temperature of hybridization and thus separation of the FAM from hemin/G-quadruplex. The liberated CRET pair causes a ratiometric increase in the donor's fluorescent signal and a decrease in the acceptor signal. Using this method, Pb ions have been measured rapidly (<15 min) with a low limit of detection at 5 nM. By removing the requirement of exogenous light excitation, we have demonstrated a simple and portable detection using a smartphone, making the DNAzyme-CRET system suitable for field tests of lake water. Since DNAzymes selective for other metal ions or targets, such as bacteria, can be obtained using in vitro selection, the method reported here opens a new avenue for rapid, portable, and ratiometric detection of many targets in environmental monitoring, food safety, and medical diagnostics.
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http://dx.doi.org/10.1021/acs.analchem.1c01077DOI Listing
July 2021

Dry Eye and Phacoemulsification Cataract Surgery: A Systematic Review and Meta-Analysis.

Front Med (Lausanne) 2021 8;8:649030. Epub 2021 Jul 8.

Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.

To evaluate whether dry eye deteriorates after phacoemulsification cataract surgery, and to explore the influential factors. Studies published before February 2020 indexed on PubMed and the Cochrane Central Register of Controlled Trials were retrieved. A meta-analysis, including meta-regression, a sensitivity analysis, and a subgroup analysis, were performed. Twenty studies with 2,247 eyes were included in the meta-analysis, dry eye-related parameters were investigated preoperatively and 1 month postoperatively. Patients with pre-existing meibomian gland dysfunction (MGD) had worsened subjective symptoms of dry eye (1.31, 95% confidence interval (CI) [0.66, 1.95], < 0.0001), a reduced tear break-up time (BUT) (-2.27, 95% CI [-2.66, -1.88], < 0.0001), and a worse corneal fluorescein staining (CFS) score (0.75, 95% CI [0.5, 1.0], < 0.0001) after phacoemulsification cataract surgery, whereas in the general population, the subjective symptoms score and CFS remained unchanged and BUT decreased slightly after surgery. Patients without diabetes showed significantly reduced total tear secretion after phacoemulsification cataract surgery (-1.25, 95% CI [-1.62, -0.88], < 0.0001). Dry eye generally remained unchanged 1 month after phacoemulsification cataract surgery. Notably, worsened symptoms and signs of dry eye were observed more frequently in patients with pre-existing MGD. Patients without diabetes were more susceptible to reduced tearing postoperatively. Identifier: PERSPERO (2020: CRD42020203316).
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http://dx.doi.org/10.3389/fmed.2021.649030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295542PMC
July 2021

Review of Associations between Built Environment Characteristics and Severe Acute Respiratory Syndrome Coronavirus 2 Infection Risk.

Int J Environ Res Public Health 2021 07 15;18(14). Epub 2021 Jul 15.

Department of Architecture and Civil Engineering, City University of Hong Kong, Kowloon Tong, Hong Kong 999077, China.

The coronavirus disease 2019 pandemic has stimulated intensive research interest in its transmission pathways and infection factors, e.g., socioeconomic and demographic characteristics, climatology, baseline health conditions or pre-existing diseases, and government policies. Meanwhile, some empirical studies suggested that built environment attributes may be associated with the transmission mechanism and infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, no review has been conducted to explore the effect of built environment characteristics on the infection risk. This research gap prevents government officials and urban planners from creating effective urban design guidelines to contain SARS-CoV-2 infections and face future pandemic challenges. This review summarizes evidence from 25 empirical studies and provides an overview of the effect of built environment on SARS-CoV-2 infection risk. Virus infection risk was positively associated with the density of commercial facilities, roads, and schools and with public transit accessibility, whereas it was negatively associated with the availability of green spaces. This review recommends several directions for future studies, namely using longitudinal research design and individual-level data, considering multilevel factors and extending to diversified geographic areas.
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http://dx.doi.org/10.3390/ijerph18147561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305984PMC
July 2021

How do we measure attention? Using factor analysis to establish construct validity of neuropsychological tests.

Cogn Res Princ Implic 2021 07 22;6(1):51. Epub 2021 Jul 22.

Basic Biobehavioral and Psychological Sciences Branch, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD, 20850, USA.

We investigated whether standardized neuropsychological tests and experimental cognitive paradigms measure the same cognitive faculties. Specifically, do neuropsychological tests commonly used to assess attention measure the same construct as attention paradigms used in cognitive psychology and neuroscience? We built on the "general attention factor", comprising several widely used experimental paradigms (Huang et al., 2012). Participants (n = 636) completed an on-line battery (TestMyBrain.org) of six experimental tests [Multiple Object Tracking, Flanker Interference, Visual Working Memory, Approximate Number Sense, Spatial Configuration Visual Search, and Gradual Onset Continuous Performance Task (Grad CPT)] and eight neuropsychological tests [Trail Making Test versions A & B (TMT-A, TMT-B), Digit Symbol Coding, Forward and Backward Digit Span, Letter Cancellation, Spatial Span, and Arithmetic]. Exploratory factor analysis in a subset of 357 participants identified a five-factor structure: (1) attentional capacity (Multiple Object Tracking, Visual Working Memory, Digit Symbol Coding, Spatial Span), (2) search (Visual Search, TMT-A, TMT-B, Letter Cancellation); (3) Digit Span; (4) Arithmetic; and (5) Sustained Attention (GradCPT). Confirmatory analysis in 279 held-out participants showed that this model fit better than competing models. A hierarchical model where a general cognitive factor was imposed above the five specific factors fit as well as the model without the general factor. We conclude that Digit Span and Arithmetic tests should not be classified as attention tests. Digit Symbol Coding and Spatial Span tap attentional capacity, while TMT-A, TMT-B, and Letter Cancellation tap search (or attention-shifting) ability. These five tests can be classified as attention tests.
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http://dx.doi.org/10.1186/s41235-021-00313-1DOI Listing
July 2021

Comparisons of intraocular lens power calculation methods for eyes with previous myopic laser refractive surgery: Bayesian network meta-analysis.

J Cataract Refract Surg 2021 08;47(8):1011-1018

From the Department of Ophthalmology and Eye Institute, Eye and ENT Hospital of Fudan University; NHC Key Laboratory of Myopia (Fudan University); Key Laboratory of Myopia, Chinese Academy of Medical Science; and Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China.

Purpose: To compare the accuracy of the methods for calculation of intraocular lens (IOL) power in eyes with previous myopic laser refractive surgery.

Setting: EENT Hospital of Fudan University, Shanghai, China.

Design: Network meta-analysis.

Methods: A literature search of MEDLINE and Cochrane Library from January 2000 to July 2019 was conducted for studies that evaluated methods of calculating IOL power in eyes with previous myopic laser refractive surgery. Outcomes measurements were the percentages of prediction error within ±0.50 diopters (D) and ±1.00 D of the target refraction (% ±0.50 D and % ±1.00 D). Traditional and network meta-analysis were conducted.

Results: Nineteen prospective or retrospective clinical studies, including 1217 eyes and 13 calculation methods, were identified. A traditional meta-analysis showed that compared with the widely used Haigis-L method, the Barrett True-K formula, optical coherence tomography (OCT), and Masket methods showed significantly higher % ±0.50 D, whereas no difference was found in the % ±1.00 D. A network meta-analysis revealed that compared with the Haigis-L method, the OCT, Barrett True-K formula, and optiwave refractive analysis (ORA) methods performed better on the % ±0.50 D, whereas the Barrett True-K formula and ORA methods performed better on the % ±1.00 D. Based on the performances of both outcomes, the Barrett True-K formula, OCT, and ORA methods showed highest probability to rank the top 3 among the 13 methods.

Conclusions: The Barrett True-K formula, OCT, and ORA methods seemed to offer greater accuracy than others in calculating the IOL power for postrefractive surgery eyes.
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http://dx.doi.org/10.1097/j.jcrs.0000000000000562DOI Listing
August 2021

Functional analysis of deleterious SNPs in lens epithelial cells.

Mol Vis 2021 1;27:403-414. Epub 2021 Jul 1.

Eye Institute, Eye & ENT Hospital of Fudan University, Shanghai, China.

Purpose: Ephrin (Eph) receptor A2 () polymorphism has been associated with age-related cataract (ARC) in different populations worldwide, but the mechanisms by which this polymorphism results in the development of ARC are unclear. Here, we chose four single nucleotide polymorphisms (SNPs; rs35903225, rs145592908, rs137853199, and rs116506614) and studied their function in human lens epithelial cells (LECs).

Methods: The four mutants were overexpressed using lentiviral transduction in human LECs. Cells expressing wild-type (WT) and mutated EPHA2 were subjected to quantitative PCR (qPCR), western blot, immunoprecipitation (IP), and transwell migration assay. MG132 and chloroquine were used to inhibit the degradation of the WT and mutated EPHA2. The structural changes induced by rs137853199 were predicted and optimized using Schrödinger software. IP-mass spectrometry (IP-MS) was performed to examine the proteins that directly interact with WT and rs137853199 EPHA2. Sanger sequencing was performed to determine the frequency of rs137853199 in 184 patients with ARC (73 cortical cataracts, 56 nuclear cataracts, and 55 posterior subcapsular cataracts) and 49 normal controls.

Results: Compared with the WT and the other three mutations, the rs137853199 mutation specifically resulted in a significant decrease in the expression of EPHA2. We identified that EPHA2 rs137853199 is degraded via the ubiquitin-proteasomal pathway through a lysine-48 (K48) residue linkage. Furthermore, the knockdown of reduced cell migration; while the overexpression of WT rescued this defect, the overexpression of rs137853199 did not. In addition, in cells overexpressing rs137853199 , the expression of β-catenin, a key protein that regulates cell migration, significantly decreased. We predicted that rs137853199 would induce a conformational change at a linker position in the carboxyl terminal of EPHA2. The IP-MS results showed that the main molecular functions of the proteins that specifically bind WT or rs137853199 EPHA2 are binding and catalysis, while the main protein class is the protein-modifying enzyme. Finally, we discovered that the minor allele frequency of rs137853199 was significantly higher in cortical cataract patients than it was in normal controls.

Conclusions: In summary, these findings suggest a mechanism by which a point mutation in disrupts protein stability, expedites protein degradation, and decreases cell mobility. Importantly, this mutant is associated with cortical cataracts.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254660PMC
July 2021

Development and validation of a new algorithm model for differential diagnosis between Crohn's disease and intestinal tuberculosis: a combination of laboratory, imaging and endoscopic characteristics.

BMC Gastroenterol 2021 Jul 13;21(1):291. Epub 2021 Jul 13.

Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, People's Republic of China.

Background: Sometimes in clinical practice, it is a great challenge to distinguish Crohn's disease (CD) and intestinal tuberculosis (ITB), we conducted this study to identify simple and useful algorithm for distinguishing them.

Methods: We retrospectively reviewed the medical history of the patients who were diagnosed as ITB or CD. We firstly identified ITB patients, and then the patients diagnosed with CD were matched by age, sex, and admission time in a 1:1 ratio. Patients who admitted between May 1, 2013 and April 30, 2019 were regarded as training cohort, and patients admitted between May 1, 2019 and May 1, 2020 were regarded as validation cohort. We used multivariate analysis to identify the potential variables, and then we used R package rpart to build the classification and regression tree (CART), and validated the newly developed model.

Results: In total, the training cohort included 84 ITB and 84 CD patients, the validation cohort included 22 ITB and 22 CD patients. Multivariate analysis showed that, positive interferon-gamma release assays (IGRAs), ≥ 4 segments involved, longitudinal ulcer, circular ulcer, and aphthous ulcer were confirmed as independent discriminating factors. Using these parameters to build the CART model made an overall accuracy rate was 88.64%, with sensitivity, specificity, NPV, and PPV being 90.91%, 86.36%, 90.48% and 86.96%, respectively.

Conclusion: We developed a simple and novel algorithm model covering laboratory, imaging, and endoscopy parameters with CART to differentiate ITB and CD with good accuracy. Positive IGRAs and circular ulcer were suggestive of ITB, while ≥ 4 segments involved, longitudinal ulcer, and aphthous ulcer were suggestive of CD.
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http://dx.doi.org/10.1186/s12876-021-01838-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276438PMC
July 2021

Experiment investigation on pulsed gamma-ray fluence rate effect on Yb-doped yttrium aluminum garnet scintillator.

Rev Sci Instrum 2021 Jun;92(6):063304

State Key Laboratory of Intense Pulsed Radiation Simulation and Effect, Northwest Institute of Nuclear Technology, Xi'an 710024, China.

As an ultrafast inorganic scintillator, Yb-doped YAlO [yttrium aluminum garnet (YAG)] crystals have potential applications in various fields, such as ultrafast radiation detection, solar neutrino detection, pulsed radiation imaging, and nuclear reaction kinetics diagnosis. In this work, the fluence rate effect of pulsed γ rays on the Yb:YAG scintillation crystal was investigated at the "QiangGuang-I" facility. The experiment results show that the fluence rate linear response upper limit of the Yb:YAG crystal is about 9.1 × 10 MeV cm s. The Yb:YAG crystal changed from colorless to yellow, and the relative light output decreased to 63% of its initial value after the irradiations, which were attributed to the radiation induced damage. It is deduced that oxygen vacancies and divalent Yb cations were generated after the irradiations.
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http://dx.doi.org/10.1063/5.0047026DOI Listing
June 2021

Biosensing with DNAzymes.

Chem Soc Rev 2021 Jul 6. Epub 2021 Jul 6.

Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario L8S 4K1, Canada.

This article provides a comprehensive review of biosensing with DNAzymes, providing an overview of different sensing applications while highlighting major progress and seminal contributions to the field of portable biosensor devices and point-of-care diagnostics. Specifically, the field of functional nucleic acids is introduced, with a specific focus on DNAzymes. The incorporation of DNAzymes into bioassays is then described, followed by a detailed overview of recent advances in the development of in vivo sensing platforms and portable sensors incorporating DNAzymes for molecular recognition. Finally, a critical perspective on the field, and a summary of where DNAzyme-based devices may make the biggest impact are provided.
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http://dx.doi.org/10.1039/d1cs00240fDOI Listing
July 2021

Characteristics of Patients and Treatment Recommendations from a Multidisciplinary Spinal Tumor Program.

Palliat Med Rep 2020 31;1(1):143-148. Epub 2020 Jul 31.

Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts, USA.

We describe characteristics of patient and treatment recommendations from a spinal tumor board at one institution, including representation from palliative care. The impact of prospective multidisciplinary input for patients with spinal tumors is poorly understood despite their increasing complexity. We retrospectively reviewed 622 cases sequentially discussed at a weekly spinal tumor board, and abstracted patient and treatment information from the medical record and meeting minutes. From April 2017 to February 2019, 622 cases representing 438 unique patients were discussed. The median age was 62 years (range 21-92). Most patients had spinal tumors originating from metastases (91.78%), including breast (14.3%), nonsmall cell lung cancer (13.4%), prostate (10.9%), and renal cell cancer (8.8%), and the remainder had primary central nervous system (4.3%) or benign tumors (3.9%). Sixty-five percent of patients were alive at last follow-up. Conventional external beam radiotherapy was the most common treatment recommendation (33.8%) followed by surgery (26.2%), stereotactic body radiation therapy (17.8%), imaging follow-up (16.6%), and vertebroplasty (15.9%). Palliative care was the primary treatment recommended for 4.5%, and no therapy recommended for 4.0%. Treatment recommendation involved two modalities for 29% of cases, and three in 1.3% of cases. In four cases, biopsy to confirm pathology changed management due to unexpected findings of osteomyelitis, hematopoiesis, or new diagnosis of plasmacytoma. Multidisciplinary input is integral to the optimal care of spinal tumor patients. The high risk of death highlights the need to prioritize modalities that optimize quality of life in the context of a patient's individual prognosis.
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http://dx.doi.org/10.1089/pmr.2020.0070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241365PMC
July 2020

Functional analysis of deleterious SNPs in lens epithelial cells.

Mol Vis 2021 23;27:384-395. Epub 2021 Jun 23.

Eye Institute, Eye & ENT Hospital of Fudan University, Shanghai, China.

Purpose: Ephrin (Eph) receptor A2 () polymorphism has been associated with age-related cataract (ARC) in different populations worldwide, but the mechanisms by which this polymorphism results in the development of ARC are unclear. Here, we chose four single nucleotide polymorphisms (SNPs; rs35903225, rs145592908, rs137853199, and rs116506614) and studied their function in human lens epithelial cells (LECs).

Methods: The four mutants were overexpressed using lentiviral transduction in human LECs. Cells expressing wild-type (WT) and mutated EPHA2 were subjected to quantitative PCR (qPCR), western blot, immunoprecipitation (IP), and transwell migration assay. MG132 and chloroquine were used to inhibit the degradation of the WT and mutated EPHA2. The structural changes induced by rs137853199 were predicted and optimized using Schrödinger software. IP-mass spectrometry (IP-MS) was performed to examine the proteins that directly interact with WT and rs137853199 EPHA2. Sanger sequencing was performed to determine the frequency of rs137853199 in 184 patients with ARC (73 cortical cataracts, 56 nuclear cataracts, and 55 posterior subcapsular cataracts) and 49 normal controls.

Results: Compared with the WT and the other three mutations, the rs137853199 mutation specifically resulted in a significant decrease in the expression of EPHA2. We identified that EPHA2 rs137853199 is degraded via the ubiquitin-proteasomal pathway through a lysine-48 (K48) residue linkage. Furthermore, the knockdown of reduced cell migration; while the overexpression of WT rescued this defect, the overexpression of rs137853199 did not. In addition, in cells overexpressing rs137853199 , the expression of β-catenin, a key protein that regulates cell migration, significantly decreased. We predicted that rs137853199 would induce a conformational change at a linker position in the carboxyl terminal of EPHA2. The IP-MS results showed that the main molecular functions of the proteins that specifically bind WT or rs137853199 EPHA2 are binding and catalysis, while the main protein class is the protein-modifying enzyme. Finally, we discovered that the minor allele frequency of rs137853199 was significantly higher in cortical cataract patients than it was in normal controls.

Conclusions: In summary, these findings suggest a mechanism by which a point mutation in disrupts protein stability, expedites protein degradation, and decreases cell mobility. Importantly, this mutant is associated with cortical cataracts.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219505PMC
June 2021

Advances in Smart Sensing and Medical Electronics by Self-Powered Sensors Based on Triboelectric Nanogenerators.

Micromachines (Basel) 2021 Jun 15;12(6). Epub 2021 Jun 15.

Faculty of Mathematics and Information Science, Southwest University, Chongqing 400700, China.

With the rapid progress of artificial intelligence, humans are moving toward the era of the intelligent connection of all things. Therefore, the demand for sensors is drastically increasing with developing intelligent social applications. Traditional sensors must be triggered by an external power source and the energy consumption is high for equipment that is widely distributed and working intermittently, which is not conducive to developing sustainable green and healthy applications. However, self-powered sensors based on triboelectric nanogenerators (TENG) can autonomously harvest energy from the surrounding environment and convert this energy into electrical energy for storage. Sensors can also be self-powered without an external power supply, which is vital for smart cities, smart homes, smart transportation, environmental monitoring, wearable devices, and bio-medicine. This review mainly summarizes the working mechanism of TENG and the research progress of self-powered sensors based on TENG about the Internet of Things (IoT), robotics, human-computer interaction, and intelligent medical fields in recent years.
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http://dx.doi.org/10.3390/mi12060698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232818PMC
June 2021

Resting-state functional magnetic resonance imaging of the cerebellar vermis in patients with Parkinson's disease and visuospatial disorder.

Neurosci Lett 2021 Jun 23;760:136082. Epub 2021 Jun 23.

Department of Geriatric Neurology, First Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province, China. Electronic address:

Purpose: Visuospatial disorders (VSDs) are common in Parkinson's disease (PD). VSDs may involve cerebellar vermis, but evidence from functional connectivity (FC) studies is lacking. Here we compared FC between cerebellar vermis and the entire brain between PD patients with or without VSD, and between patients and healthy controls.

Methods: Resting-state 3.0-T functional magnetic resonance imaging was performed on 19 controls, 31 PD patients with VSD and 12 PD patients without VSD. Correlations in brain network were calculated between eight regions of interest in the cerebellar vermis (I-VIII) and other voxels in the brain, and voxel-based FC was analyzed. Patients were assessed in terms of cognitive function as well as motor and non-motor symptoms.

Results: In both types of patients, cerebellar vermis VIII, IX and X showed positive FC with the default-mode network (DMN), executive control network and sensorimotor network. Cerebellar vermis I and II showed positive FC with the visual network and DMN in controls, but negative FC in PD patients without VSD. Cerebellar vermis X showed negative FC with lobules VIII and IX of the left cerebellar hemisphere in controls, but positive FC in PD patients with VSD.

Conclusion: Positive FC connecting the cerebellar vermis VIII and X with associated brain networks in PD patients with VSD may be compensatory activation. PD may involve disruption of functional coupling between the cerebellar vermis and cerebral cortex.
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http://dx.doi.org/10.1016/j.neulet.2021.136082DOI Listing
June 2021

A Novel Hierarchical Deep Learning Framework for Diagnosing Multiple Visual Impairment Diseases in the Clinical Environment.

Front Med (Lausanne) 2021 7;8:654696. Epub 2021 Jun 7.

Complete Genomics Inc., San Jose, CA, United States.

Early detection and treatment of visual impairment diseases are critical and integral to combating avoidable blindness. To enable this, artificial intelligence-based disease identification approaches are vital for visual impairment diseases, especially for people living in areas with a few ophthalmologists. In this study, we demonstrated the identification of a large variety of visual impairment diseases using a coarse-to-fine approach. We designed a hierarchical deep learning network, which is composed of a family of multi-task & multi-label learning classifiers representing different levels of eye diseases derived from a predefined hierarchical eye disease taxonomy. A multi-level disease-guided loss function was proposed to learn the fine-grained variability of eye disease features. The proposed framework was trained for both ocular surface and retinal images, independently. The training dataset comprised 7,100 clinical images from 1,600 patients with 100 diseases. To show the feasibility of the proposed framework, we demonstrated eye disease identification on the first two levels of the eye disease taxonomy, namely 7 ocular diseases with 4 ocular surface diseases and 3 retinal fundus diseases in level 1 and 17 subclasses with 9 ocular surface diseases and 8 retinal fundus diseases in level 2. The proposed framework is flexible and extensible, which can be inherently trained on more levels with sufficient training data for each subtype diseases (e.g., the 17 classes of level 2 include 100 subtype diseases defined as level 3 diseases). The performance of the proposed framework was evaluated against 40 board-certified ophthalmologists on clinical cases with various visual impairment diseases and showed that the proposed framework had high sensitivity and specificity with the area under the receiver operating characteristic curve ranging from 0.743 to 0.989 in identifying all identified major causes of blindness. Further assessment of 4,670 cases in a tertiary eye center also demonstrated that the proposed framework achieved a high identification accuracy rate for different visual impairment diseases compared with that of human graders in a clinical setting. The proposed hierarchical deep learning framework would improve clinical practice in ophthalmology and broaden the scope of service available, especially for people living in areas with a few ophthalmologists.
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http://dx.doi.org/10.3389/fmed.2021.654696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215208PMC
June 2021

Integrative Cistromic and Transcriptomic Analyses Identify CREB Target Genes in Cystic Renal Epithelial Cells.

J Am Soc Nephrol 2021 Jun 23. Epub 2021 Jun 23.

Y Chen, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Institute of Urology, Tianjin, China

Genome-wide mapping of transcription factor (TF) binding sites is essential to identify a TF's direct target genes in kidney development and diseases. However, due to the cellular complexity of the kidney and limited numbers of a given cell type, it has been challenging to determine the binding sites of a TF in vivo. cAMP-response element-binding protein (CREB) is phosphorylated and hyperactive in autosomal dominant polycystic kidney disease (ADPKD). We focus on CREB as an example to profile genomic loci bound by a TF and to identify its target genes using low numbers of specific kidney cells. Cleavage under targets and release using nuclease (CUT&RUN) assays were performed with agglutinin (DBA)-positive tubular epithelial cells from normal and ADPKD mouse kidneys. Pharmacological inhibition of CREB with 666-15 and genetic inhibition with A-CREB were undertaken using ADPKD mouse models. CUT&RUN to profile genome-wide distribution of phosphorylated CREB (p-CREB) indicated correlation of p-CREB binding with active histone modifications (H3K4me3 and H3K27ac) in cystic epithelial cells. Integrative analysis with CUT&RUN and RNA-sequencing revealed CREB direct targets, including genes involved in ribosome biogenesis and protein synthesis. Pharmacological and genetic inhibition of CREB suppressed cyst growth in ADPKD mouse models. CREB promotes cystogenesis by activating ribosome biogenesis genes. CUT&RUN, coupled with transcriptomic analysis, enables interrogation of TF binding and identification of direct TF targets from a low number of specific kidney cells.
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http://dx.doi.org/10.1681/ASN.2021010101DOI Listing
June 2021

Identification of a Locus Near Associated With Progression-Free Survival in Ovarian Cancer.

Cancer Epidemiol Biomarkers Prev 2021 Jun 23. Epub 2021 Jun 23.

Gynecologic Oncology Center, Kiel, Germany.

Background: Many loci have been found to be associated with risk of epithelial ovarian cancer (EOC). However, although there is considerable variation in progression-free survival (PFS), no loci have been found to be associated with outcome at genome-wide levels of significance.

Methods: We carried out a genome-wide association study (GWAS) of PFS in 2,352 women with EOC who had undergone cytoreductive surgery and standard carboplatin/paclitaxel chemotherapy.

Results: We found seven SNPs at 12q24.33 associated with PFS ( < 5 × 10), the top SNP being rs10794418 (HR = 1.24; 95% CI, 1.15-1.34; = 1.47 × 10). High expression of a nearby gene, , is associated with shorter PFS in EOC, and with poor prognosis in other cancers. SNP rs10794418 is also associated with expression of in ovarian tumors, with the allele associated with shorter PFS being associated with higher expression, and chromatin interactions were detected between the promoter and associated SNPs in serous and endometrioid EOC cell lines. ULK1 knockout ovarian cancer cell lines showed significantly increased sensitivity to carboplatin .

Conclusions: The locus at 12q24.33 represents one of the first genome-wide significant loci for survival for any cancer. is a plausible candidate for the target of this association.

Impact: This finding provides insight into genetic markers associated with EOC outcome and potential treatment options..
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1817DOI Listing
June 2021

PNA-Assisted DNAzymes to Cleave Double-Stranded DNA for Genetic Engineering with High Sequence Fidelity.

J Am Chem Soc 2021 Jul 22;143(26):9724-9728. Epub 2021 Jun 22.

DNAzymes have been widely used in many sensing and imaging applications but have rarely been used for genetic engineering since their discovery in 1994, because their substrate scope is mostly limited to single-stranded DNA or RNA, whereas genetic information is stored mostly in double-stranded DNA (dsDNA). To overcome this major limitation, we herein report peptide nucleic acid (PNA)-assisted double-stranded DNA nicking by DNAzymes (PANDA) as the first example to expand DNAzyme activity toward dsDNA. We show that PANDA is programmable in efficiently nicking or causing double strand breaks on target dsDNA, which mimics protein nucleases and can act as restriction enzymes in molecular cloning. In addition to being much smaller than protein enzymes, PANDA has a higher sequence fidelity compared with CRISPR/Cas under the condition we tested, demonstrating its potential as a novel alternative tool for genetic engineering and other biochemical applications.
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http://dx.doi.org/10.1021/jacs.1c03129DOI Listing
July 2021

Bio-Guided Fractionation and Molecular Networking Reveal Fatty Acids to Be Principal Anti-Parasitic Compounds in Nordic Seaweeds.

Front Pharmacol 2021 2;12:674520. Epub 2021 Jun 2.

Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.

Widespread use of antimicrobial drugs has led to high levels of drug-resistance in pathogen populations and a need for novel sources of anti-bacterial and anti-parasitic compounds. Macroalgae (seaweed) are potentially a rich source of bioactive compounds, and several species have traditionally been used as vermifuges. Here, we investigated the anti-parasitic properties of four common cold-water Nordic seaweeds; (Rhodophyta), , and (Ochrophyta, Phaeophyceae). Screening of organic extracts against helminths of swine () and sheep () revealed that and had particularly high biological activity. A combination of molecular networking and bio-guided fractionation led to the isolation of six compounds from extracts of these two species identified in both fermented and non-fermented samples. The six isolated compounds were tentatively identified by using MS-FINDER as five fatty acids and one monoglyceride: Stearidonic acid (), Eicosapentaenoic acid (), Alpha-Linolenic acid (), Docosahexaenoic acid (), Arachidonic acid (), and Monoacylglycerol (MG 20:5) (). Individual compounds showed only modest activity against , but a clear synergistic effect was apparent when selected compounds were tested in combination. Collectively, our data reveal that fatty acids may have a previously unappreciated role as natural anti-parasitic compounds, which suggests that seaweed products may represent a viable option for control of intestinal helminth infections.
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http://dx.doi.org/10.3389/fphar.2021.674520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206555PMC
June 2021

Taurine promotes the production of CD4CD25FOXP3 Treg cells through regulating IL-35/STAT1 pathway in a mouse allergic rhinitis model.

Allergy Asthma Clin Immunol 2021 Jun 19;17(1):59. Epub 2021 Jun 19.

Department of Otorhinolaryngology, Head and Neck Surgery, Dahua Hospital, Laohumin Road No. 901, Shanghai, 200237, China.

Background: Allergic rhinitis (AR) is one of the most widespread immune conditions worldwide. However, common treatments often present with significant side effects or are cost-prohibitive for much of the population. A plethora of treatments have been used for the treatment of AR including antihistamines, steroids, and immune modulators. Among the treatments which have shown potential for efficacy in treating AR with a minimum of side effects but remains understudied is the conditionally essential amino acid taurine. Taurine has been previously shown to reduce AR symptoms. Here, we examine the role of taurine in modulating T regulatory cells, modulating the cytokine response in AR, and restoring healthy nasal mucosa.

Methods: Blood samples from 20 healthy donors and 20 AR patients were compared for CD4CD25FoxP3 T regulatory (Treg) cell population percentage, cytokine release, and STAT1 signaling with and without taurine treatment or IL-35 neutralization. An OVA-induced AR mouse model was administered vehicle, taurine, or taurine plus an IL-35 neutralizing antibody and assayed for sneezing frequency, inflammatory cytokine response, nasal mucosa goblet cell density, and T regulatory cell percentage. CD4 cells were further examined for cytokine release, STAT1 phosphorylation, and response to an anti-IL-35 antibody with and without a STAT1 inhibitor.

Results: Comparison of blood from normal donors and AR patients showed a reduction in CD4CD25FoxP3 Treg cells in AR patients and a strong correlation between Treg percentage and IL-35 release. A similar pattern of Treg suppression was found in untreated AR mice when compared to normal control mice wherein there was a reduction in Treg percentage and a corresponding decrease in IL-35 release. AR mice also demonstrated increased sneezing frequency, an infiltration of goblet cell in nasal mucosa, and a reduction in IL-35 release from CD4 cells. Conversely, IL-4, IL-5, and IL-13 secretion from CD4 cells were increased in AR model mice, as was STAT1 phosphorylation. When AR mice were treated with taurine, sneezing frequency and nasal mucosa goblet cell content were reduced while Treg abundance was increased to that of normal mice. Accordingly, IL-35 release was restored, while IL-4, IL-5, and IL-13 secretion from CD4 cells were suppressed. Likewise, STAT1 phosphorylation was inhibited with taurine treatment. Taurine-treated mice also given an IL-35 neutralizing antibody exhibited AR pathology including frequent sneezing and high nasal goblet cell content while retaining a restoration of Tregs. Furthermore, murine AR model CD4 cells exposed to recombinant IL-35 responded with a reduction in inflammatory cytokine release and a decrease in STAT1 phosphorylation, mimicking the effect of taurine treatment.

Conclusions: Taurine induces release of IL-35 in AR; IL-35 promotes the production of CD4CD25FoxP3 Treg cells via a STAT1-dependent pathway. The restoration of Treg populations by taurine normalizes the inflammatory response, reduces AR symptomology, and reduces histopathologic signs of AR.
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http://dx.doi.org/10.1186/s13223-021-00562-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214264PMC
June 2021

Viewing time and facial trustworthiness perception: Giving it a second thought may not work for older adults.

Psych J 2021 Jun 16. Epub 2021 Jun 16.

School of Psychological and Cognitive Sciences, Peking University, Beijing, China.

Older adults tend to rate unfamiliar faces higher on trustworthiness than do their younger counterparts. Although the saying goes "look before you leap", it is still unknown whether such a strategy could also apply to facial trustworthiness perception, and our understanding of the time course in facial trustworthiness perception also remains unclear. Here, we have argued that a cognitive controlled process suggested by "socioemotional selectivity theory" could potentially lead to such biased trustworthiness perception. Two experiments were conducted to test the association between viewing time and trustworthiness perception. The first study used hierarchical linear modeling in a sample of younger (N = 30, M  = 20.53, SD = 1.61, 50% female) and older (N = 30, M  = 63.27, SD = 3.14, 43% female) adults, and found that viewing time and trustworthiness evaluation were positively associated. Using the same stimuli, our second study further manipulated viewing time by two levels (500 ms vs. 3000 ms) and compared younger (N = 28, M  = 23.93, SD = 2.68, 50% female) and older (N = 30, M  = 64.47, SD = 4.32, 50% female) adults' facial trustworthiness evaluation. As expected, a significant three-way interaction revealed that viewing time only impacted older adults' facial trustworthiness evaluation, and only when given shorter viewing time did older adults show similar facial trustworthiness ratings as younger adults. The present study is the first to directly investigate the relationship between older adults' viewing time on unfamiliar faces and their perception of facial trustworthiness. Findings suggested that a second thought in facial perception may not benefit older adults' trustworthiness evaluation.
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http://dx.doi.org/10.1002/pchj.469DOI Listing
June 2021
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