Publications by authors named "Linlin Gao"

64 Publications

THAN: task-driven hierarchical attention network for the diagnosis of mild cognitive impairment and Alzheimer's disease.

Quant Imaging Med Surg 2021 Jul;11(7):3338-3354

Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Background: To assist doctors to diagnose mild cognitive impairment (MCI) and Alzheimer's disease (AD) early and accurately, convolutional neural networks based on structural magnetic resonance imaging (sMRI) images have been developed and shown excellent performance. However, they are still limited in their capacity in extracting discriminative features because of large sMRI image volumes yet small lesion regions and the small number of sMRI images.

Methods: We proposed a task-driven hierarchical attention network (THAN) taking advantage of the merits of patch-based and attention-based convolutional neural networks for MCI and AD diagnosis. THAN consists of an information sub-network and a hierarchical attention sub-network. In the information sub-network, an information map extractor, a patch-assistant module, and a mutual-boosting loss function are designed to generate a task-driven information map, which automatically highlights disease-related regions and their importance for final classification. In the hierarchical attention sub-network, a visual attention module and a semantic attention module are devised based on the information map to extract discriminative features for disease diagnosis.

Results: Extensive experiments were conducted for four classification tasks: MCI versus () normal controls (NC), AD NC, AD MCI, and AD MCI NC. Results demonstrated that THAN attained the accuracy of 81.6% for MCI NC, 93.5% for AD NC, 80.8% for AD MCI, and 62.9% for AD MCI NC. It outperformed advanced attention-based and patch-based methods. Moreover, information maps generated by the information sub-network could highlight the potential biomarkers of MCI and AD, such as the hippocampus and ventricles. Furthermore, when the visual and semantic attention modules were combined, the performance of the four tasks was highly improved.

Conclusions: The information sub-network can automatically highlight the disease-related regions. The hierarchical attention sub-network can extract discriminative visual and semantic features. Through the two sub-networks, THAN fully exploits the visual and semantic features of disease-related regions and meanwhile considers global features of sMRI images, which finally facilitate the diagnosis of MCI and AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/qims-21-91DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249997PMC
July 2021

Alteration of brain structural connectivity in progression of Parkinson's disease: A connectome-wide network analysis.

Neuroimage Clin 2021 Jun 6;31:102715. Epub 2021 Jun 6.

Department of Neurobiology, Neurology and Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Disease, Beijing, China. Electronic address:

Pinpointing the brain dysconnectivity in idiopathic rapid eye movement sleep behaviour disorder (iRBD) can facilitate preventing the conversion of Parkinson's disease (PD) from prodromal phase. Recent neuroimage investigations reported disruptive brain white matter connectivity in both iRBD and PD, respectively. However, the intrinsic process of the human brain structural network evolving from iRBD to PD still remains largely unknown. To address this issue, 151 participants including iRBD, PD and age-matched normal controls were recruited to receive diffusion MRI scans and neuropsychological examinations. The connectome-wide association analysis was performed to detect reorganization of brain structural network along with PD progression. Eight brain seed regions in both cortical and subcortical areas demonstrated significant structural pattern changes along with the progression of PD. Applying machine learning on the key connectivity related to these seed regions demonstrated better classification accuracy compared to conventional network-based statistic. Our study shows that connectome-wide association analysis reveals the underlying structural connectivity patterns related to the progression of PD, and provide a promising distinct capability to predict prodromal PD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nicl.2021.102715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209844PMC
June 2021

Current status and future prospects of grapevine anthracnose caused by Elsinoe ampelina: An important disease in humid grape-growing regions.

Mol Plant Pathol 2021 Aug 7;22(8):899-910. Epub 2021 Jun 7.

State Key Laboratory of Crop Stress Biology in Arid Areas, College of Horticulture, Northwest A&F University, Yangling, China.

Anthracnose, caused by Elsinoe ampelina, is one of the most destructive diseases of grapevines worldwide, especially in humid areas. E. ampelina mainly infects young tissues starting from shoots to berries and affects vine vigour and berry yield. The occurrence and the role of the sexual stage in the disease cycle and the grapevine-E. ampelina interaction remain poorly understood. However, the recent genome sequence data of E. ampelina provides the basis for further studies to understand its evolution, pathogenicity mechanisms, and effector repertoire. New studies on E. ampelina have been conducted in recent years. In this pathogen profile, we present a comprehensive literature review of E. ampelina to summarize the findings on its aetiology, infection mechanisms, genome, pathogenicity, and host resistance.

Taxonomy: Elsinoe ampelina Shear; Kingdom Fungi; Phylum Ascomycota; Subphylum Pezizomycotina; Class Dothideomycetes; Subclass Dothideomycetidae; Order Myriangiales Starbäck; Family Elsinoaceae Höhnel; Genus Elsinoe Racib.

Host Range: E. ampelina only infects Vitis species and hybrids.

Distribution: The grapevine anthracnose is distributed worldwide but is most prevalent in Argentina, Australia, Brazil, Canada, China, India, Japan, Korea, New Zealand, South Africa, Thailand, USA, and Uruguay.

Disease Symptoms: E. ampelina causes slightly abundant depressed spots on young leaves, petioles, stems, tendrils, rachises, and berries. Under severe infection conditions, early defoliation, berry dropping, and delayed berry development and ripening may occur.

Genome: The genomes of two E. ampelina isolates, YL-1 and CECT 20119, are publicly released with 8,057 and 10,207 predicted genes, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/mpp.13076DOI Listing
August 2021

Atlas of breast cancer infiltrated B-lymphocytes revealed by paired single-cell RNA-sequencing and antigen receptor profiling.

Nat Commun 2021 04 12;12(1):2186. Epub 2021 Apr 12.

National Institute of Biological Sciences, Beijing, China.

To gain mechanistic insights into the functions and developmental dynamics of tumor-infiltrated immune cells, especially B-lymphocytes, here we combine single-cell RNA-sequencing and antigen receptor lineage analysis to characterize a large number of triple-negative breast cancer infiltrated immune cells and report a comprehensive atlas of tumor-infiltrated B-lymphocytes. The single-cell transcriptional profiles reveal significant heterogeneity in tumor-infiltrated B-cell subgroups. The single-cell antigen receptor analyses demonstrate that compared with those in peripheral blood, tumor-infiltrated B-cells have more mature and memory B-cell characteristics, higher clonality, more class switching recombination and somatic hypermutations. Combined analyses suggest local differentiation of infiltrated memory B-cells within breast tumors. The B-cell signatures based on the single-cell RNA-sequencing results are significantly associated with improved survival in breast tumor patients. Functional analyses of tumor-infiltrated B-cell populations suggest that mechanistically, B-cell subgroups may contribute to immunosurveillance through various pathways. Further dissection of tumor-infiltrated B-cell populations will provide valuable clues for tumor immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-22300-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042001PMC
April 2021

Neonatal Hyperoxia Downregulates Claudin-4, Occludin, and ZO-1 Expression in Rat Kidney Accompanied by Impaired Proximal Tubular Development.

Oxid Med Cell Longev 2020 2;2020:2641461. Epub 2020 Dec 2.

Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.

Hyperoxia is essential to manage in preterm infants but causes injury to immature kidney. Previous study indicates that hyperoxia causes oxidative damage to neonatal kidney and impairs renal development. However, the underlying mechanisms by which neonatal hyperoxia effects on immature kidney still need to be elucidated. Tight junction, among which the representative proteins are claudin-4, occludin, and ZO-1, plays a crucial role in nephrogenesis and maintaining renal function. Inflammatory cytokines are involved in the pleiotropic regulation of tight junction proteins. Here, we investigated how neonatal hyperoxia affected the expression of key tight junction proteins and inflammatory factors (IL-6 and TNF-) in the developing rat kidneys and elucidated their correlation with renal injury. We found claudin-4, occludin, and zonula occludens-1 (ZO-1) expression in proximal tubules was significantly downregulated after neonatal hyperoxia. The expression of these tight junction proteins was positively correlated with that of IL-6 and TNF-, while claudin-4 expression was positively correlated with injury score of proximal tubules in mature kidneys. These findings indicated that impaired expression of tight junction proteins in kidney might be a potential mechanism of hyperoxia-induced nephrogenic disorders. It provides new insights to further study oxidative renal injury and development disorders and will be helpful for seeking potential therapeutics for hyperoxia-induced renal injury in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/2641461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725566PMC
December 2020

CircSMYD4 regulates proliferation, migration and apoptosis of hepatocellular carcinoma cells by sponging miR-584-5p.

Cancer Cell Int 2020 Nov 19;20(1):556. Epub 2020 Nov 19.

Department of Medical Oncology, Jiaozuo People's Hospital, No. 267, Middle Jiefang Road, Shanyang District, Jiaozuo, 454002, China.

Background: There is evidence that circSMYD4 is differentially expressed in hepatocellular carcinoma (HCC), but its mechanism of action remains unclear. Therefore, this study aimed to explore the role of circSMYD4 in the occurrence and development of HCC and its specific molecular mechanism.

Methods: The expressions of related genes and proteins in the development of HCC were detected by real-time quantitative-PCR and Western blot. HCC cells treated with RNase R and Actinomycin D were used to examine the stability of circSMYD4. Bioinformatics analysis, RNA pull-down assay, luciferase assay and Spearman correlation analysis were performed to evaluate the interaction between circSMYD4 and miRNA. Cell Counting Kit-8, clone formation assay, wound healing assay, Transwell, flow cytometry, nude tumor formation experiment, and immunohistochemistry were employed to analyze the function of circSMYD4 in HCC. A rescue experiment was conducted to analyze the effect of miR-584-5p on the physiological functions of cells.

Results: CircSMYD4 was down-regulated in HCC tissues and cells, and was not easily affected by RNase R and Actinomycin D. The abundances of circSMYD4 and SMYD4 in the cytoplasm were significantly higher than in the nucleus. Up-regulation of circSMYD4 inhibited the proliferation, invasion and migration and promoted the apoptosis of HCC cells in vitro, while it inhibited tumor growth, promoted apoptosis-related proteins, and suppressed alpha-fetoprotein (AFP) levels in vivo. CircSMYD4 could be used as a miRNA sponge to target miR-584-5p. In addition, miR-584-5p overexpression partially reversed the regulatory effect of circSMYD4 on HCC.

Conclusion: CircSMYD4 prevents the development of HCC through regulating multiple signaling pathways such as metastasis and apoptosis by sponging miR-584-5p.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12935-020-01648-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678128PMC
November 2020

Transcriptome Analysis of the Grape- Pathosystem Reveals Novel Effectors and a Robust Defense Response.

Mol Plant Microbe Interact 2021 Jan 23;34(1):110-121. Epub 2020 Nov 23.

State Key Laboratory of Crop Stress Biology in Arid Areas, College of Horticulture, Northwest A&F University, Yangling, Shaanxi 712100, China.

is an ascomycetous fungus that causes grape anthracnose, a potentially devastating disease worldwide. In this study, a dual RNA-seq analysis was used to simultaneously monitor the fungal genes related to pathogenesis and grape genes related to defense during the interaction at 2, 3, 4, and 5 days postinoculation. Consistent with their potential roles in pathogenicity, genes for carbohydrate-active enzymes, secondary metabolite synthesis, pathogen-host interaction, and those encoding secreted proteins are upregulated during infection. Based on -mediated transient assays in , we further showed that eight and nine candidate effectors, respectively, suppressed BAX- and INF1-mediated programmed cell death. The host response was characterized by the induction of multiple defense systems against , including synthesis of phenylpropanoids, stilbenes, and terpenoid biosynthesis, cell-wall modifications, regulation by phytohormones, and expression of defense-related genes. Together, these findings offer new insights into molecular mechanisms underlying the grape- interaction.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1094/MPMI-08-20-0227-RDOI Listing
January 2021

Long non-coding RNA HCG18 promotes M1 macrophage polarization through regulating the miR-146a/TRAF6 axis, facilitating the progression of diabetic peripheral neuropathy.

Mol Cell Biochem 2021 Jan 29;476(1):471-482. Epub 2020 Sep 29.

Department of Endocrinology and Metabolism, The Second Clinical Medical College of Shanxi Medical University, The Second Hospital of Shanxi Medical University, No. 382, WuYi Road, Taiyuan City, 030001, Shanxi Province, China.

Diabetic peripheral neuropathy (DPN) is one of the most important complications in diabetes mellitus (DM), which has been reported to be modulated by long non-coding RNAs (lncRNAs). The purpose of the current study is to explore the regulatory mechanism of lncRNA HCG18 on DPN in vitro. The expression of lncRNA HCG18, miR-146a, TRAF6, CD11c, and iNOS was detected by qRT-PCR. Through Enzyme-linked immunosorbent assay, the levels of inflammatory factors (TNF-α, IL-1β, and IL-6) were determined. M1 macrophage polarization was measured by flow cytometry analysis. The interactions between miR-146a and HCG18/TRAF6 were predicted by Starbase/Targetscan software and verified by the dual luciferase reporter assay. Western blot assay was performed to determine the protein expression of TRAF6. LncRNA HCG18 was highly expressed in DPN model and HG-induced macrophages. The levels of inflammatory factors (TNF-α, IL-1β, and IL-6) were elevated in DPN model. The expression of M1 markers (CD11c and iNOS) was visibly up-regulated in DPN model and was positively correlated with HCG18 expression. LncRNA HCG18 facilitated M1 macrophage polarization. In addition, miR-146a was identified as a target of lncRNA HCG18. Overexpression of miR-146a reversed the promoting effect of HCG18 on M1 macrophage polarization. Simultaneously, TRAF6 was a target gene of miR-146a TRAF6 expression was positively modulated by HCG18 and was negatively modulated by miR-146a. Down-regulation of TRAF6 reversed the promoting effect of HCG18 on M1 macrophage polarization. LncRNA HCG18 promotes M1 macrophage polarization via regulating the miR-146a/TRAF6 axis, facilitating the progression of DPN. This study provides a possible therapeutic strategy for DPN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11010-020-03923-3DOI Listing
January 2021

High-level MYC expression associates with poor survival in patients with acute myeloid leukemia and collaborates with overexpressed p53 in leukemic transformation in patients with myelodysplastic syndrome.

Int J Lab Hematol 2021 Feb 19;43(1):99-109. Epub 2020 Aug 19.

Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.

Introduction: Patients with mutated and overexpressed p53 have an aggressive course in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Studies on the impact of MYC expression in AML are limited. This is the first study to evaluate MYC expression and p53 status in AML and MDS.

Methods: We identified 214 patients, 101 AML, 79 MDS, and 34 negative control patients. We retrospectively assessed p53 and MYC expression by immunohistochemistry and correlated MYC expression with p53 expression and aberrational status of TP53.

Results: The level of both p53 and MYC expression was significantly higher in AML (mean: 9.7%; 12.1%) and MDS (mean: 5.2%; 5.5%) patients compared with control cases (mean: 0.18%; 2.3%; P = .001-0.02). p53 and MYC expression levels were even more elevated in AML when compared to MDS patients (P < .001). MYC expression was significantly associated with p53 expression and TP53 aberration in AML patients but not in MDS patients (P < .001). p53 expression and >20% MYC expression showed an adverse impact on overall survival (OS) (P < .05) in AML patients while p53 but not MYC expression showed an adverse impact on OS in MDS patients. MYC and p53 dual expression, as well as combined MYC expression and TP53 aberration, showed negative impact on OS in AML patients. MDS patients with leukemic transformation revealed an interval increase in expression of both p53 and MYC.

Conclusion: High-level MYC expression associates with p53 abnormality and poor survival in AML. MYC may provide proliferative advantage for leukemic progression in p53 dependent and independent manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijlh.13316DOI Listing
February 2021

Correction to: DNA typing from skeletal remains: a comparison between capillary electrophoresis and massively parallel sequencing platforms.

Int J Legal Med 2020 Nov;134(6):2037

School of Forensic Medicine, Shanxi Medical University, Taiyuan, 030001, China.

The name of an author was misspelled. The correct spelling is "Linlin Gao" instead of Linin Gao.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00414-020-02342-9DOI Listing
November 2020

Structural and functional brain alterations in patients with idiopathic rapid eye movement sleep behavior disorder.

J Neuroradiol 2020 Jun 12. Epub 2020 Jun 12.

Department of Neurobiology, Neurology and Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing Institute of Geriatrics, Beijing, China; Clinical Center for Parkinson's Disease, Capital Medical University, Beijing, China; Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing Key Laboratory for Parkinson's Disease, Parkinson Disease Center of Beijing Institute for Brain Disorders, Beijing, China; National Clinical Research Center for Geriatric Disorders, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China. Electronic address:

Objective: To investigate structural and functional alterations in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) compared with healthy controls.

Methods: Twenty-seven patients with polysomnography-confirmed iRBD and 33 healthy subjects were recruited. All subjects underwent a 3-tesla structural and resting-state functional magnetic resonance imaging (fMRI) examination. Voxel-based morphometry (VBM) analysis was performed to assess grey matter alterations between groups. The amplitude of low-frequency fluctuations (ALFF) was calculated and then compared to measure differences in spontaneous brain activity. Correlations were performed to explore associations between imaging metrics and clinical characteristics in iRBD patients.

Results: Compared with healthy controls, patients with iRBD had decreased grey matter volume in the frontal, temporal, parietal, occipital cortices as well as increased grey matter volume in cerebellum posterior lobe, putamen, and thalamus. Patients with iRBD also exhibited increased ALFF values in the right parahippocampal gyrus. Olfaction correlated with ALFF value changes in occipital cortices.

Conclusions: Patients with iRBD had widespread decreases of grey matter volume. Increases of grey matter volume in cerebellum, putamen, and thalamus may suggest a compensatory effect, while the altered ALFF values in parahippocampal gyrus and occipital cortices may play a role in the underlying process of neurodegeneration in this disorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neurad.2020.04.007DOI Listing
June 2020

DNA typing from skeletal remains: a comparison between capillary electrophoresis and massively parallel sequencing platforms.

Int J Legal Med 2020 Nov 7;134(6):2029-2035. Epub 2020 Jun 7.

School of Forensic Medicine, Shanxi Medical University, Taiyuan, 030001, China.

Skeletal remains encountered frequently in forensic applications are a challenging specimen, since their DNA is usually degraded due to harsh conditions, limiting the utilization of skeletal DNA. Forensic scientists have tried various methods to extract DNA from skeletal remains of low quantity and poor quality or improve detecting technology for more information from compromised DNA. Compared with traditional capillary electrophoresis (CE), massively parallel sequencing (MPS) is more sensitive to shorter fragments, able to detect allele sequences for variations from core motif or flanking regions, and able to detect more markers with a higher discrimination power. In this study, short tandem repeats (STR) and single nucleotide polymorphisms (SNP) from 35 human skeletons were genotyped by MPS platform, and CE method was also used to perform STR genotyping. The results indicated that the detection rates reached 100.00% in 16 of 35 samples with MPS method, while the same 100.00% was reached in only 9 samples with CE. The success rates of MPS were also higher than that of CE method in shared 21 loci (excluding Y-indel, DYS391, and SE33), especially in loci detected by MPS method only. Besides, all SNPs (124 and 90 SNPs in males and females) were detected in 18 samples of 35 samples by MPS method. Some intra-allelic sequence variants were observed in eight loci (D21S11, D8S1179, D5S2800, D3S1358, vWA, D2S1338, D1S1656, D12S391) using MPS technology. Interestingly, there is a sample showing genotyping disagreement in FGA locus. The clone sequencing verified that a "T" deletion discovered in flanking sequence of FGA led to wrong genotyping on Ampliseq Converge. Our results indicated that MPS could be adopted in qualified labs as a supplementary when the DNA of skeletal remains are hard to identify.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00414-020-02327-8DOI Listing
November 2020

Single-Cell RNA Sequencing to Dissect the Immunological Network of Autoimmune Myocarditis.

Circulation 2020 Jul 20;142(4):384-400. Epub 2020 May 20.

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (X.H., Y.C., Y.H., X.C., J.S.).

Background: Myocarditis can develop into dilated cardiomyopathy, which may require heart transplantation. The immunological network of myocarditis phases remains unknown. This study aimed to investigate the immunological network during the transition from myocarditis to cardiomyopathy and to identify the genes contributing to the inflammatory response to myocarditis.

Methods: Mice were treated with myosin heavy chain-α peptides to generate an experimental autoimmune myocarditis (EAM) model. We performed single-cell RNA sequencing analysis of cells extracted from mouse hearts during different EAM phases, including normal control, acute inflammatory, subacute inflammatory, and myopathy phases. Human heart tissues were collected from the surgically removed hearts of patients who had undergone heart transplantation.

Results: We identified 26 cell subtypes among 34 665 cells. Macrophages constituted the main immune cell population at all disease phases (>60%), and an inflammation-associated macrophage cluster was identified in which the expression of -regulated genes was upregulated. The neutrophil population was increased after the induction of EAM, and neutrophils then released to participate in the EAM process. T cells were observed at the highest percentage at the subacute inflammatory phase. T-helper 17 cells, in which the expression of -regulated genes was upregulated, constituted the main T-cell population detected at the acute inflammatory phase, whereas regulatory T cells were the main T-cell population detected at the subacute inflammatory phase, and γδ T cells releasing were the main T-cell population observed at the myopathy phase. Moreover, the expression level correlated with the extent of inflammation. In addition, PX-478 could alleviate the inflammatory responses of the different EAM phases. Last, was expressed at higher levels in patients with acute autoimmune myocarditis than in patients with dilated cardiomyopathy and healthy control subjects.

Conclusions: We present here a comprehensive single-cell landscape of the cardiac immune cells in different EAM phases. In addition, we elucidate the contribution of to the inflammatory response through the regulation of immune cell activity, particularly of macrophage cluster 2 and T-helper 17 cells. Moreover, an inhibitor alleviated inflammatory cell infiltration of the EAM model and may serve as a potential therapeutic target in the clinic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.119.043545DOI Listing
July 2020

Dysregulation in the Unfolded Protein Response in the FGR Rat Pancreas.

Int J Endocrinol 2020 20;2020:5759182. Epub 2020 Jan 20.

Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang 110004, China.

Accumulating evidence suggests that fetal growth restriction (FGR) leads to the development of diabetes mellitus in adults. The aim of this study was to investigate the effect of protein malnutrition on the pancreatic unfolded protein response (UPR) pathway in FGR offspring. An FGR model was developed by feeding a low-protein diet to pregnant rats throughout gestation. Eighty-four UPR pathway components in the pancreas were investigated by quantitative PCR arrays and confirmed by qPCR and western blotting. Activating transcription factor (Atf4 and Atf6), herpud1, protein kinase R-like endoplasmic reticulum kinase (Perk), X-box binding protein 1 (Xbp1), and the phosphorylation of eIF2 were upregulated, while cyclic AMP-responsive element-binding protein 3-like protein was markedly downregulated in FGR fetuses compared with controls. Investigation in adult offspring revealed temporal changes, for most UPR factors restored to normal, except that dysregulation of Atf6 and Creb3l3 maintained until adulthood. Moreover, autophagy was suppressed in FGR fetal pancreas and may be associated with decreased activation of AMP-activated protein kinase (Ampk). Apoptosis regulators Bax and cleaved-caspase 3 and 9 were upregulated in FGR fetal pancreas. Given that islet size and number were decreased in FGR fetus, we speculated that the aberrant intrauterine milieu impaired UPR signaling in fetal pancreas development. Whether these alterations early in life contribute to the predisposition of FGR fetuses to adult metabolic disorders invites further exploration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/5759182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201628PMC
January 2020

Discriminative Feature Network Based on a Hierarchical Attention Mechanism for Semantic Hippocampus Segmentation.

IEEE J Biomed Health Inform 2021 02 5;25(2):504-513. Epub 2021 Feb 5.

The morphological analysis of hippocampus is vital to various neurological studies including brain disorders and brain anatomy. To assist doctors in analyzing the shape and volume of the hippocampus, an accurate and automatic hippocampus segmentation method is highly demanded in the clinical practice. Given that fully convolutional networks (FCNs) have made significant contributions in biomedical image segmentation applications, we propose a notably discriminative feature network based on a hierarchical attention mechanism in hippocampal segmentation. First, considering the problem that the hippocampus is a rather small part in MR images, we design a context-aware high-level feature extraction module (CHFEM) to extract high-level features of scale invariance in the encoder stage. Further, we introduce a hierarchical attention mechanism into our segmentation framework. The mechanism is divided into three parts: a low-level feature spatial attention module (LFSAM) is developed to learn the spatial relationship between different pixels on each channel in the low-level stage of the encoder, a high-level feature channel attention module (HFCAM) is to model the semantic information relationship on different channel images in the high-level stage of the encoder, and a cross-connected attention module (CCAM) is designed in the decoder part to further suppress the noisy boundaries of hippocampus and simultaneously utilize the attentional low-level features from the encoder to better guide the high-level hippocampus edge segmentation in the decoder phase. The proposed approach achieves outstanding performance on the ADNI dataset and the Decathlon dataset compared with other semantic segmentation models and existing hippocampal segmentation approaches. Source code is available at https://github.com/LannyShi/Hippocampal-segmentation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/JBHI.2020.2994114DOI Listing
February 2021

[Detection of a BRCA1 c.2013_2014ins GT variant an ethnic Han Chinese pedigree affected with breast cancer].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Apr;37(4):415-418

Department of Head, Neck and Breast Surgery, Xinxiang Central Hospital, Henan 453000, China.

Objective: To detect potential variant in an ethical Han Chinese pedigree affected with breast cancer.

Methods: The proband and her relatives were subjected to next-generation sequencing using a target capture sequencing kit containing 121 cancer-related genes. Candidate variants were selected by analysis of their type, frequency in population, and segregation with the phenotype. Candidate variant was verified by Sanger sequencing and TA cloning.

Results: A c.2013_2014ins GT variant was detected in the BRCA1 gene among all breast cancer patients from this pedigree but not among healthy females. The variant was not recorded in the 1000 Genome Project database or the Exome Aggregation Consortium (ExAC) database. The frameshifting insertion was predicted to form an premature stop codon in gene transcript and can give rise to a truncated protein.

Conclusion: The BRCA1 c.2013_2014ins GT variant probably underlies the pathogenesis of breast cancer in this Chinese pedigree.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2020.04.012DOI Listing
April 2020

Genome Sequence Resource for , the Causal Organism of Grapevine Anthracnose.

Mol Plant Microbe Interact 2020 Apr 3;33(4):576-579. Epub 2020 Mar 3.

State Key Laboratory of Crop Stress Biology in Arid Areas, College of Horticulture, Northwest A&F University, Yangling, Shaanxi 712100, China.

is an ascomycetous fungus that causes grape anthracnose, a potentially devastating disease worldwide. Here, we report a 28.29 Mb high-quality genome sequence of YL-1 that encodes 8,057 predicted protein-coding genes and represents the first sequenced genome assembly of . This study adds to the current genomic resources for the genus and paves the way for research on comparative genomic studies, -grape interactions, and improvement of management strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1094/MPMI-12-19-0337-ADOI Listing
April 2020

Quantitative evaluation of iron content in idiopathic rapid eye movement sleep behavior disorder.

Mov Disord 2020 03 17;35(3):478-485. Epub 2019 Dec 17.

School of Electronic and Information Engineering, Harbin Institute of Technology at Shenzhen, Shenzhen, Guangdong, China.

Background: Idiopathic rapid eye movement sleep behavior disorder is an early sign of neurodegenerative disease. This study aimed to quantitatively evaluate iron content in idiopathic rapid eye movement sleep behavior disorder patients using quantitative susceptibility mapping and to examine the potential of this technique to identify the prodromal stage of α-synucleinopathies.

Methods: Twenty-five idiopathic rapid eye movement sleep behavior disorder patients, 32 Parkinson's disease patients, and 50 healthy controls underwent quantitative susceptibility mapping. The mean magnetic susceptibility values within the bilateral substantia nigra, globus pallidus, red nucleus, head of the caudate nucleus, and putamen were calculated and compared among groups. The relationships between the values and the clinical features of idiopathic rapid eye movement sleep behavior disorder and Parkinson's disease were measured using correlation analysis.

Results: Idiopathic rapid eye movement sleep behavior disorder patients had elevated iron in the bilateral substantia nigra compared with healthy controls. Parkinson's disease patients had increased iron in the bilateral substantia nigra, globus pallidus, and left red nucleus compared with healthy controls and had elevated iron levels in the bilateral substantia nigra compared with idiopathic rapid eye movement sleep behavior disorder patients. Mean magnetic susceptibility values were positively correlated with disease duration in the left substantia nigra in idiopathic rapid eye movement sleep behavior disorder patients.

Conclusions: Quantitative susceptibility mapping can detect increased iron in the substantia nigra in idiopathic rapid eye movement sleep behavior disorder, which becomes more significant as the disorder progresses. This technique has the potential to be an early objective neuroimaging marker for detecting α-synucleinopathies. © 2019 International Parkinson and Movement Disorder Society.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mds.27929DOI Listing
March 2020

The Endophytic Fungus from Wild Grape as an Antagonist of and Other Grape Pathogens.

Phytopathology 2020 Apr 11;110(4):843-850. Epub 2020 Feb 11.

State Key Laboratory of Crop Stress Biology in Arid Areas, College of Horticulture, Northwest A&F University, Yangling, Shaanxi 712100, China.

Gray mold, caused by , is one of the most prevalent fungal diseases in table and wine grapes, affecting grape quality and yields. In this study, we isolated several endophytic fungi, including , , sp., and , from leaves of Amur grape () cultivar Shuangyou and investigated their biocontrol activity against . In vitro dual assay showed that isolate SYE-1 inhibited growth of . The isolate also had a wide range of biocontrol activity against and . Mycelial growth and conidium germination of were significantly inhibited by metabolites of in agar plates and culture extracts of from liquid culture. The isolate produced a total chitinase activity of 0.4 U/ml after incubation for 10 days in Czapek's liquid medium. In addition, application of culture extracts of prior to inoculation significantly reduced disease severity on grape leaves of the susceptible cultivar Red Globe. Taken together, our results indicate that has potential as a biocontrol agent to control grape gray mold.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1094/PHYTO-09-19-0347-RDOI Listing
April 2020

Label-Free Proteomics of the Fetal Pancreas Identifies Deficits in the Peroxisome in Rats with Intrauterine Growth Restriction.

Oxid Med Cell Longev 2019 3;2019:1520753. Epub 2019 Nov 3.

Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China.

Aim: The objective of the present study was to identify differentially expressed proteins (DEPs) in the pancreas of a fetus with intrauterine growth restriction (IUGR) and to investigate the molecular mechanisms leading to adulthood diabetes in IUGR.

Methods: The IUGR rat model was induced by maternal protein malnutrition. The fetal pancreas was collected at embryonic day 20 (E20). Protein was extracted, pooled, and subjected to label-free quantitative proteomic analysis. Bioinformatics analysis (GO and IPA) was performed to define the pathways and networks associated with DEPs. LC-MS results were confirmed by western blotting and/or quantitative PCR (q-PCR). The principal parameters of oxidative stress-superoxide dismutase (Sod) were determined in blood samples of fetal rats.

Results: A total of 57 DEPs (27 upregulated, 30 downregulated) were identified with a 1.5-fold change threshold and a value ≤ 0.05 between the IUGR and the control pancreas. Bioinformatics analysis revealed that these proteins play important roles in peroxisome biogenesis and fission, fatty acid beta-oxidation (FAO), mitotic cell cycle, and histone modification. The peroxin Pex14 was downregulated in the IUGR pancreas as confirmed by western blotting and q-PCR. Pmp70, a peroxisomal membrane protein involved in the transport of fatty acids, was upregulated. Hsd17b4 and Acox1/2, which catalyze different steps of peroxisomal FAO, were dysregulated. Sod plasma concentrations in the IUGR fetus were higher than those in the control, suggesting partial compensation for oxidative stress. Multiple DEPs were related to the regulation of the cell cycle, including reduced Cdk1, Mcm2, and Brd4. The histone acetylation regulators Hdac1/2 were downregulated, whereas Sirt1/3 and acetylated H3K56 were increased in the IUGR fetal pancreas.

Conclusion: The present study identified DEPs in the fetal pancreas of IUGR rats by proteomic analysis. Downregulation of pancreas peroxins and dysregulation of enzymes involved in peroxisomal FAO may impair the biogenesis and function of the peroxisome and may underlie the development of T2 diabetes mellitus in adult IUGR rats. Disorders of cell cycle regulators may induce cell division arrest and lead to smaller islets. The present data provide new insight into the role of the peroxisome in the development of the pancreas and may be valuable in furthering our understanding of the pathogenesis of IUGR-induced diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/1520753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874927PMC
April 2020

Clinical features and visual prognostic indicators after vitrectomy for Terson syndrome.

Eye (Lond) 2020 04 27;34(4):650-656. Epub 2019 Aug 27.

Eye Center, The Second Hospital of Jilin University, #218 Ziqiang Street, Changchun, 130000, Jilin, China.

Purpose: To determine clinical characteristics and identify factors associated with better visual outcomes in patients who had vitrectomy for vitreous haemorrhage (VH) associated with Terson syndrome (TS).

Methods: The records of 48 patients (54 corresponding eyes) who underwent vitrectomy for VH associated with TS from January 2008 to December 2017 were retrospectively reviewed. The main outcome measure was the final postoperative visual acuity.

Results: At the last visit, 34 eyes (63.0%) achieved a BCVA of 0.3 or better. Eyes associated with traumatic brain injury had a better visual outcome than those with primary intracerebral haemorrhage (P = 0.042). In the primary intracerebral haemorrhage group, patients with hypertension-induced intracranial haemorrhage (IH) showed poorer final visual acuities than the ruptured intracranial aneurysm group (P = 0.023). In the delayed vitrectomy group, epiretinal membrane and peripheral retina changes were more common (P < 0.05). However, the difference in final visual acuity between the early and delayed vitrectomy groups was not significant (P = 0.69).

Conclusion: Most of the patients obtained visual recovery after vitrectomy for TS. VH associated with ruptured intracranial aneurysm or traumatic brain injury or eyes without retinal haemorrhage are predictive of better prognosis. Although the timing of vitrectomy was not related to the final postoperative visual outcome, early vitrectomy by three months seems to suggest less epiretinal membrane formation, retinal tears, and retinal detachments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41433-019-0547-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093525PMC
April 2020

Berberine reduces neuroglia activation and inflammation in streptozotocin-induced diabetic mice.

Int J Immunopathol Pharmacol 2019 Jan-Dec;33:2058738419866379

Department of Internal Medicine, Jinan Second People's Hospital, Jinan, China.

We aimed to analyze the action of berberine on the neuropathic pain and neuroglia activation in experimental diabetes mellitus (DM) model. Diabetes in mice was induced by intraperitoneal injection of streptozotocin (STZ) followed by the administration of berberine. Mechanical allodynia and thermal hyperalgesia and activations of microglia and astrocytes were evaluated. The levels of pro-inflammatory cytokines and protein expressions of inflammatory proteins were assessed by enzyme-linked immunosorbent assay (ELISA) and western blot, respectively. Our results revealed the anti-nociceptive effects of berberine in DM mice, supported by the improved mechanical threshold and thermal latency. In addition, berberine suppressed the activations of microglia and astrocytes in the spinal cords of diabetic mice. Berberine inhibited the expression of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and interleukin-1β (IL-1β), along with inflammatory proteins including iNOS and COX-2. Berberine suppressed neuropathic pain in STZ-induced diabetic mice, and this effect is related to the reduction on the neuroglia activation and inflammation associated with DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2058738419866379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657114PMC
January 2020

Repetitive Transcranial Magnetic Stimulation Does Not Improve the Sequence Effect in Freezing of Gait.

Parkinsons Dis 2019 4;2019:2196195. Epub 2019 Jun 4.

Department of Neurobiology, Key Laboratory on Neurodegenerative Disorders of Ministry of Education, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing, China.

Introduction: The sequence effect (SE) is a reason contributing to freezing of gait (FOG) in Parkinson's disease (PD) patients. There is no effective treatment for the SE. The objective of the current study is to investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the SE in PD patients with FOG.

Methods: 28 PD patients with FOG received either real or sham 10-Hz rTMS over the supplementary motor area (SMA). The effects of rTMS on the SE, FOG, and some gait parameters were evaluated.

Results: rTMS did not improve the SE. Real rTMS had beneficial effects on FOG and some gait parameters, and this effect lasted for at least four weeks.

Conclusions: High-frequency rTMS over the SMA cannot alleviate the SE in PD patients with FOG. rTMS has a long-lasting beneficial effect on FOG; however, this effect is not achieved by improving the SE but may be through improving some other gait parameters.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/2196195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589230PMC
June 2019

Fully automatic knee osteoarthritis severity grading using deep neural networks with a novel ordinal loss.

Comput Med Imaging Graph 2019 07 13;75:84-92. Epub 2019 Jun 13.

J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, United States. Electronic address:

Knee osteoarthritis (OA) is one major cause of activity limitation and physical disability in older adults. Early detection and intervention can help slow down the OA degeneration. Physicians' grading based on visual inspection is subjective, varied across interpreters, and highly relied on their experience. In this paper, we successively apply two deep convolutional neural networks (CNN) to automatically measure the knee OA severity, as assessed by the Kellgren-Lawrence (KL) grading system. Firstly, considering the size of knee joints distributed in X-ray images with small variability, we detect knee joints using a customized one-stage YOLOv2 network. Secondly, we fine-tune the most popular CNN models, including variants of ResNet, VGG, and DenseNet as well as InceptionV3, to classify the detected knee joint images with a novel adjustable ordinal loss. To be specific, motivated by the ordinal nature of the knee KL grading task, we assign higher penalty to misclassification with larger distance between the predicted KL grade and the real KL grade. The baseline X-ray images from the Osteoarthritis Initiative (OAI) dataset are used for evaluation. On the knee joint detection, we achieve mean Jaccard index of 0.858 and recall of 92.2% under the Jaccard index threshold of 0.75. On the knee KL grading task, the fine-tuned VGG-19 model with the proposed ordinal loss obtains the best classification accuracy of 69.7% and mean absolute error (MAE) of 0.344. Both knee joint detection and knee KL grading achieve state-of-the-art performance. The code, dataset, and models are released at https://github.com/PingjunChen/KneeAnalysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.compmedimag.2019.06.002DOI Listing
July 2019

PKCζ facilitates lymphatic metastatic spread of prostate cancer cells in a mice xenograft model.

Oncogene 2019 05 31;38(22):4215-4231. Epub 2019 Jan 31.

Department of Medical Biosciences, Building 6M, 2:nd floor, Umeå University, SE 90185, Umeå, Sweden.

Prostate cancer disseminates primarily into the adjacent lymph nodes, which is related to a poor outcome. Atypical protein kinase C ζ (PKCζ) is highly expressed in aggressive prostate cancer and correlates with Gleason score, clinical stage, and poor prognosis. Here, we report the molecular mechanisms of PKCζ in lymphatic metastasis during prostate cancer progression. Using zinc-finger nuclease technology or PKCζ shRNA lentiviral particles, and orthotopic mouse xenografts, we show that PKCζ-knockout or knockdown from aggressive prostate cancer (PC3 and PC3U) cells, decreasesd tumor growth and lymphatic metastasis in vivo. Intriguingly, PKCζ-knockout or knockdown impaired the activation of AKT, ERK, and NF-κB signaling in prostate cancer cells, thereby impairing the expression of lymphangiogenic factors and macrophage recruitment, resulting in aberrant lymphangiogenesis. Moreover, PKCζ regulated the expression of hyaluronan synthase enzymes, which is important for hyaluronan-mediated lymphatic drainage and tumor dissemination. Thus, PKCζ plays a crucial oncogenic role in the lymphatic metastasis of prostate cancer and is predicted to be a novel therapeutic target for prostate cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41388-019-0722-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756056PMC
May 2019

Neuroprotective effects of dexmedetomidine against isoflurane-induced neuronal injury via glutamate regulation in neonatal rats.

Drug Des Devel Ther 2019 21;13:153-160. Epub 2018 Dec 21.

Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang 110004, China,

Background: Considerable evidences support the finding that the anesthesia reagent isoflurane increases neuronal cell death in young rats. Recent studies have shown that dexmedetomidine can reduce isoflurane-induced neuronal injury, but the mechanism remains unclear. We investigated whether isoflurane cause neurotoxicity to the central nervous system by regulating the N-methyl-D-aspartate receptor (NMDAR) and excitatory amino acid transporter1 (EAAT1) in young rats. Furthermore, we examined if dexmedetomidine could decrease isoflurane-induced neurotoxicity.

Methods: Neonatal rats (postnatal day 7, n=144) were randomly divided into four groups of 36 animals each: control (saline injection without isoflurane); isoflurane (2% for 4 h); isoflurane + single dose of dexmedetomidine (75 µg/kg, 20 min before the start of 2% isoflurane for 4 h); and isoflurane + dual doses of dexmedetomidine (25 µg/kg, 20 min before and 2 h after start of isoflurane at 2% for 4 h). Six neonates from each group were euthanatized at 2 h, 12 h, 24 h, 3 days, 7 days and 28 days post-anesthesia. Hippocampi were collected and processed for protein extraction. Expression levels of the NMDAR subunits NR2A and NR2B, EAAT1 and caspase-3 were measured by western blot analysis.

Results: Protein levels of NR2A, EAAT1 and caspase-3 were significantly increased in hippocampus of the isoflurane group from 2 h to 3 days, while NR2B levels were decreased. However, the -induced increase in NR2A, EAAT1 and caspase-3 and the decrease in NR2B in isoflurane-exposed rats were ameliorated in the rats treated with single or dual doses of dexmedetomidine. Isoflurane-induced neuronal damage in neonatal rats is due in part to the increase in NR2A and EAAT1 and the decrease in NR2B in the hippocampus.

Conclusion: Dexmedetomidine protects the brain against the use of isoflurane through the regulation of NR2A, NR2B and EAAT1. However, using the same amount of dexmedetomidine, the trend of protection is basically the same.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DDDT.S163197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306062PMC
May 2019

Maternal Protein Restriction Induces Alterations in Hepatic Unfolded Protein Response-Related Molecules in Adult Rat Offspring.

Front Endocrinol (Lausanne) 2018 20;9:676. Epub 2018 Nov 20.

Department of Obstetrics and Gynaecology, Shengjing Hospital of China Medical University, Shenyang, China.

Intrauterine growth restriction (IUGR) leads to the development of metabolic syndrome in adulthood. To explore the potential mechanisms of metabolic imprinting, we investigated the effect of malnutrition on hepatic unfolded protein response (UPR)-related genes in IUGR offspring. An IUGR rat model was developed by feeding a low-protein diet to pregnant rats. The expression levels and activity of hepatic UPR genes were analysed by quantitative PCR (qPCR) arrays and western blotting. The hepatic UPR molecules heat-shock 70-kDa protein 4l (), mitogen-activated protein kinase 10 (), and endoplasmic reticulum to nucleus signalling 2 () were markedly downregulated in IUGR foetuses, but the expression of and returned to normal levels at 3 weeks postnatal. In contrast, cAMP responsive element binding protein 3-like 3 () was upregulated in hepatic tissues at embryo 20(E20), then restored to normal in adulthood (12 weeks). The protein levels of activating transcription factor 2 (Atf2) and Atf6, two key factors of the UPR pathway, were upregulated in the livers of IUGR foetuses, and the latter remained upregulated until 12 weeks. Combined with our previous findings showing an increase in hepatic gluconeogenesis enzymes in IUGR offspring, we speculated that aberrant intrauterine milieu impaired UPR signalling in hepatic tissues; these alterations early in life might contribute to the predisposition of IUGR foetuses to adult metabolic disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2018.00676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262354PMC
November 2018

The Expression of Shh, Ptch1, and Gli1 in the Developing Caudal Spinal Cord of Fetal Rats With Anorectal Malformations.

J Surg Res 2019 01 29;233:173-182. Epub 2018 Aug 29.

Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. Electronic address:

Background: Postoperative incontinence and constipation still remain the major complications of anorectal malformations (ARMs), despite improvements in their treatment. One of the most important factors that affect postoperative anorectal function is malformations in the lumbosacral spinal cord. However, far too little attention has been paid to the underlying mechanism that produces these malformations.

Materials And Methods: The levels of sonic hedgehog (Shh), patched homolog 1 (Ptch1), and zinc finger-containing transcription factors 1 (Gli1) expression were investigated in the lumbosacral spinal cord in ethylenethiourea-exposed rat fetus with ARMs, and Shh, Ptch1, and Gli1 expression was confirmed with immunohistochemical staining, quantitative real-time polymerase chain reaction, and western blot analyses during lumbosacral spinal cord development both in the ARMs and normal rat embryos.

Results: Our results have shown that Shh, Ptch1, and Gli1 expression in the lumbosacral spinal cord of rat embryos with ARMs was decreased at both the messenger RNA and protein levels, when compared with their expression levels in normal tissues (P < 0.05).

Conclusions: This study demonstrated that the expression of Shh, Ptch1, and Gli1 in lumbosacral spinal cord was remarkably reduced during late developmental stages in fetal rats with ARMs. These findings offered some important insights into the involvement of the Shh-Ptch1-Gli1 signaling pathway in the pathogenesis of lumbosacral spinal cord maldevelopment in rat fetus with ARMs, which leads to complications after procedures for ARMs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jss.2018.08.006DOI Listing
January 2019

Doxorubicin-Loaded Dextran-Modified GoldMag Nanoparticles for Targeting Hepatocellular Carcinoma.

J Biomed Nanotechnol 2018 Jun;14(6):1135-1146

Doxorubicin (Dox) is one of the most widely used chemotherapeutic agents for many types of cancer, including hepatocellular carcinoma. However, clinical applications of Dox are limited due to its non-selective cytotoxicity that results in severe adverse effects. To tackle this problem targeted delivery of Dox exclusively to tumour milieu has become clinically prioritised. In this study, we first synthesized and validated Dextran coated GoldMag Nanoparticles (DGMNs) as a potential delivery vehicle for Dox. We then evaluated the cytotoxicity of Dox-DGMNs, the drug and carrier composites, under guidance of external magnetic field (EMF) in hepatocellular carcinoma cell lines and in tumour grafts. Intriguingly, DGMNs exhibited the capacity to prolong Dox release in vitro; hence, Dox-DGMNs significantly enhanced the therapeutic efficiency of the drug in vitro and in vivo, especially under EMF. However, DGMNs were able to significantly decrease systemic adverse effects and inhibit tumour growth compared to the intravenous application of free Dox. Molecular analysis revealed that tumour cells were more affected by Dox-DGMNs with EMF than Dox-DGMNs or Dox alone in terms of apoptosis and DNA damage marker expression. Overall, DGMNs exhibited a substantial potential to serve as a promising drug delivery carrier for magnetically targeted cancer therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1166/jbn.2018.2547DOI Listing
June 2018

A direct isothermal amplification system adapted for rapid SNP genotyping of multifarious sample types.

Biosens Bioelectron 2018 Sep 11;115:70-76. Epub 2018 May 11.

College of Life Sciences, Northwest University, Xi'an 710069, China; Shaanxi Provincial Engineering Research Center for Nano-Biomedical Detection, Xi'an 710077, China; National Engineering Research Center for Miniaturized Detection System, Xi'an 710069, China. Electronic address:

Genotyping of single nucleotide polymorphisms (SNPs) in point-of-care (POC) settings could be further improved through simplifying the treatment of samples. In this study, we devised an accurate, rapid and easy-to-use SNP detection system based on direct loop-mediated isothermal amplification (LAMP) without DNA extraction, known as Direct-LAMP. Samples from various sources (including whole blood, dried blood spot, buccal swab and saliva), treated with NaOH, can be used directly in amplification. The turnaround time was about 30 min from sample collection to provision of results. The accuracy was evaluated by assessing the polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and aldehyde dehydrogenase-2 (ALDH2) Glu504Lys, which are better known for their critical role in folate and ethanol metabolism, respectively. Completely consistent genotyping results reveal that Direct-LAMP is generally concordant with sequencing. This system can serve as a very promising platform in the fields of disease predisposition, drug metabolism and personalized medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bios.2018.05.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126597PMC
September 2018