Publications by authors named "Yue Guan"

176 Publications

An ultrasensitive disposable sandwich-configuration electrochemical immunosensor based on [email protected] composites and AuPt-MB for alpha-fetoprotein detection.

Bioelectrochemistry 2021 May 23;141:107846. Epub 2021 May 23.

Department of Clinical Laboratory, the Affiliated Pudong Hospital, Fudan University, Shanghai, China. Electronic address:

Early finding and diagnosis are critical for prevention and treatment of hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is a typical biomarker of HCC. Since AFP level can reflect the severity of HCC, it is essential to ensure the accurate detection of AFP. In this study, through a combination of the advantages exhibited by ordered mesoporous carbon (OMC)@gold nanoparticles (AuNPs) composites and AuPt-methylene blue (AuPt-MB), a disposable ultrasensitive sandwich-configuration electrochemical immunosensor for determination of AFP was designed. Characterized by excellent conductivity, highly ordered pore distribution and great surface area, OMC can be effective in promoting electron transfer and loading a large number of AuNPs. In the meantime, AuNPs can also immobilize AFP-Ab through Au-N bonds. As a new redox-active species, rod-like AuPt-MB demonstrates high conductivity, uniform morphology and excellent biocompatibility, which makes it capable not only to fix AFP-Ab, but also to release electrochemical signals. A wide linearity of 10 fg mL-100 ng mL and a low detection limit of 3.33 fg mL (S/N = 3) were obtained. Moreover, the proposed immunosensor exhibited acceptable selectivity, high stability and reproducibility. The excellent performance in detecting serum samples endows the proposed immunosensor with broad prospects of extensive application in the detection of disease biomarkers.
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http://dx.doi.org/10.1016/j.bioelechem.2021.107846DOI Listing
May 2021

and the Volatile of Attenuate Chronic Myocardial Ischemia Injury in a Pig Model: A Metabonomic Approach for the Mechanism Study.

Oxid Med Cell Longev 2021 28;2021:8840896. Epub 2021 Apr 28.

National Drug Clinical Trial Institute, The Second Affiliated Hospital, Shaanxi University of Chinese Medicine, Xianyang 712000, China.

(SM) coupled with (DO) has been used to relieve cardiovascular diseases in China for many years. Our previous studies have integrated that SM-the volatile oil of DO (SM-DOO)-has a cardioprotective effect on chronic myocardial ischemia based on a pharmacological method, but the cardioprotective mechanism has not been elucidated completely in the metabonomic method. In the present study, a metabonomic method based on high-performance liquid chromatography time-of-flight mass spectrometry (HPLC-Q-TOF-MS) was performed to evaluate the effects of SM-DOO on chronic myocardial ischemia induced by an ameroid constrictor, which was placed on the left anterior descending coronary artery (LAD) of pigs. Pigs were divided into three groups: sham, model, and SM-DOO group. With multivariate analysis, a clear cluster among the different groups was obtained and the potential biomarkers were recognized. These biomarkers were mainly related to energy metabolism, glucose metabolism, and fatty acid metabolism. Furthermore, the protein expressions of phosphorylated AMP-activated protein kinase (p-AMPK) and glucose transporter-4 (GLUT4) were significantly upregulated by SM-DOO. The result indicated that SM-DOO could regulate the above biomarkers and metabolic pathways, especially energy metabolism and glucose metabolism. By analyzing and verifying the biomarkers and metabolic pathways, further understanding of the cardioprotective effect of SM-DOO with its mechanism was evaluated. Metabonomic is a reliable system biology approach for understanding the cardioprotective effects of SM-DOO on chronic myocardial ischemia and elucidating the mechanism underlying this protective effect.
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http://dx.doi.org/10.1155/2021/8840896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099511PMC
April 2021

LncRNA ABCC6P1 promotes proliferation and migration of papillary thyroid cancer cells via Wnt/β-catenin signaling pathway.

Ann Transl Med 2021 Apr;9(8):664

Department of Endocrinology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Background: LncRNAs play an important regulatory function in the occurrence and progression of papillary thyroid cancer (PTC). This study aimed to investigate the role and mechanism of ATP binding cassette subfamily C member 6 pseudogene 1 (ABCC6P1) in PTC.

Methods: Cancerous and paracancer normal thyroid tissues were collected from 18 patients with PTC, who were operated at the Second Affiliated Hospital of Harbin Medical University. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to investigate the levels of ABCC6P1. Cell proliferation was evaluated using Cell Counting Kit-8 (CCK-8) and colony formation assays. Wound healing and Transwell invasion assays were performed to examine cell migratory and invasive ability. Western blotting analysis was used to detect the expression levels of EMT-related markers and Wnt/β-catenin signaling pathway-related proteins.

Results: The expression of ABCC6P1 was upregulated in PTC tissues and cells. ABCC6P1 silencing could significantly suppress the proliferation, colony formation ability, migratory and invasive ability in PTC cells. Moreover, knockdown of ABCC6P1 induced cell cycle arrest at G0/G1 phase and inhibited epithelial-mesenchymal transition (EMT) process of PTC cells by increasing the E-cadherin expression, but downregulating N-cadherin and vimentin expression. In addition, knockdown of ABCC6P1 caused a significant decrease in levels of Wnt/β-catenin signaling pathway members (including β-catenin, c-myc, and cyclin D1) in PTC cells.

Conclusions: Our study confirms that ABCC6P1 exerts an oncogenic activity in PTC which may be mediated by the Wnt/β-catenin pathway, suggesting that ABCC6P1 may be a promising therapeutic target for PTC.
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http://dx.doi.org/10.21037/atm-21-505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106106PMC
April 2021

CIHH protects the heart against left ventricular remodelling and myocardial fibrosis by balancing the renin-angiotensin system in SHR.

Life Sci 2021 Aug 27;278:119540. Epub 2021 Apr 27.

Department of Physiology, Hebei Medical University, 361, Zhongshan East Road, Shijiazhuang, Hebei Province 050017, China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang 050000, China. Electronic address:

Aim: The aim of our study was to clarify the cardioprotection of chronic intermittent hypobaric hypoxia (CIHH) and the underlying mechanism in spontaneously hypertensive rats (SHR).

Main Methods: Adult male rats were divided into normal blood pressure Wistar-Kyoto rats (WKY) control (WKY-CON), WKY rats with CIHH treatment (WKY-CIHH), SHR control (SHR-CON) and SHR with CIHH treatment (SHR-CIHH) groups. SHR-CIHH and WKY-CIHH rats were subjected to hypobaric hypoxia simulating 4000-m altitude for 35 days, 5 h per day. Arterial blood pressure and cardiac function parameters, including ejection fraction, fractional shortening and left ventricular (LV) wall thickness, were evaluated. Cardiac pathomorphology and myocardial fibrosis were determined. The expression of angiotensin-converting enzyme (ACE), ACE2, Ang II, Ang1-7, AT1 receptor, Mas receptor, IL-6, TNF-α,IL-10, SOD and MDA were assayed in myocardium.

Key Findings: CIHH significantly decreased arterial blood pressure, alleviated LV hypertrophy, and improved cardiovascular function in SHR (P < 0.05-0.01). Also, CIHH protected SHR heart against morphological changes and fibrosis. In addition, CIHH significantly down-regulated the ACE/Ang II/AT1 receptor axis and up-regulated the ACE2/Ang1-7/Mas axis of renin-angiotensin system (RAS) in SHR (P < 0.05-0.01). CIHH significantly reduced IL-6, TNF-α, and MDA levels, but increased IL-10 and SOD in SHR myocardium (P < 0.05-0.01).

Significance: The CIHH treatment protected the heart of SHR against LV remodelling and myocardial fibrosis, which might be carried out through a balance in the ACE/Ang II/AT1 axis and the ACE2/Ang1-7/Mas axis of the RAS to reduce inflammation, and inhibit oxidative stress.
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http://dx.doi.org/10.1016/j.lfs.2021.119540DOI Listing
August 2021

Chronic Intermittent Hypobaric Hypoxia Decreases High Blood Pressure by Stabilizing the Vascular Renin-Angiotensin System in Spontaneously Hypertensive Rats.

Front Physiol 2021 24;12:639454. Epub 2021 Mar 24.

Department of Physiology, Hebei Medical University, Shijiazhuang, China.

Background And Aims: Previous studies have demonstrated the anti-hypertensive effect of chronic intermittent hypobaric hypoxia (CIHH) in hypertensive rats. The present study investigated the anti-hypertensive effect of CIHH in spontaneously hypertensive rats (SHR) and the role of the renin-angiotensin system (RAS) in anti-hypertensive effect of CIHH.

Methods: Fifteen-week-old male SHR and WKY rats were divided into four groups: the SHR without CIHH treatment (SHR-CON), the SHR with CIHH treatment (SHR-CIHH), the WKY without CIHH treatment (WKY-CON), and the WKY with CIHH treatment (WKY-CIHH) groups. The SHR-CIHH and WKY-CIHH rats underwent 35-days of hypobaric hypoxia simulating an altitude of 4,000 m, 5 h per day. Arterial blood pressure and heart rate were recorded by biotelemetry, and angiotensin (Ang) II, Ang1-7, interleukin (IL)-6, tumor necrosis factor-alpha (TNF)-α, and IL-10 in serum and the mesenteric arteries were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. The microvessel tension recording technique was used to determine the contraction and relaxation of the mesenteric arteries. Hematoxylin and eosin and Masson's staining were used to observe vascular morphology and fibrosis. Western blot was employed to detect the expression of the angiotensin-converting enzyme (ACE), ACE2, AT1, and Mas proteins in the mesenteric artery.

Results: The biotelemetry result showed that CIHH decreased arterial blood pressure in SHR for 3-4 weeks ( < 0.01). The ELISA and immunohistochemistry results showed that CIHH decreased Ang II, but increased Ang1-7 in serum and the mesenteric arteries of SHR. In the CIHH-treated SHR, IL-6 and TNF-α decreased in serum and the mesenteric arteries, and IL-10 increased in serum ( < 0.05-0.01). The microvessel tension results revealed that CIHH inhibited vascular contraction with decreased Ang1-7 in the mesenteric arteries of SHR ( < 0.05-0.01). The staining results revealed that CIHH significantly improved vascular remodeling and fibrosis in SHR. The western blot results demonstrated that CIHH upregulated expression of the ACE2 and Mas proteins, and downregulated expression of the ACE and AT1 proteins ( < 0.05-0.01).

Conclusion: CIHH decreased high blood pressure in SHR, possibly by inhibiting RAS activity, downregulating the ACE-Ang II-AT1 axis and upregulating the ACE2-(Ang1-7)-Mas axis, which resulted in antagonized vascular remodeling and fibrosis, reduced inflammation, and enhanced vascular relaxation.
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http://dx.doi.org/10.3389/fphys.2021.639454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024534PMC
March 2021

Value of contrast-enhanced CT texture analysis in predicting IDH mutation status of intrahepatic cholangiocarcinoma.

Sci Rep 2021 Mar 25;11(1):6933. Epub 2021 Mar 25.

Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008, Jiangsu Province, China.

To explore the value of contrast-enhanced CT texture analysis in predicting isocitrate dehydrogenase (IDH) mutation status of intrahepatic cholangiocarcinomas (ICCs). Institutional review board approved this study. Contrast-enhanced CT images of 138 ICC patients (21 with IDH mutation and 117 without IDH mutation) were retrospectively reviewed. Texture analysis was performed for each lesion and compared between ICCs with and without IDH mutation. All textural features in each phase and combinations of textural features (p < 0.05) by Mann-Whitney U tests were separately used to train multiple support vector machine (SVM) classifiers. The classification generalizability and performance were evaluated using a tenfold cross-validation scheme. Among plain, arterial phase (AP), portal venous phase (VP), equilibrium phase (EP) and Sig classifiers, VP classifier showed the highest accuracy of 0.863 (sensitivity, 0.727; specificity, 0.885), with a mean area under the receiver operating characteristic curve of 0.813 in predicting IDH mutation in validation cohort. Texture features of CT images in portal venous phase could predict IDH mutation status of ICCs with SVM classifier preoperatively.
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http://dx.doi.org/10.1038/s41598-021-86497-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994625PMC
March 2021

Early-life phenanthrene exposure inhibits reproductive ability in adult zebrafish and the mechanism of action.

Chemosphere 2021 Jun 13;272:129635. Epub 2021 Jan 13.

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, PR China; Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, Xiamen University, Xiamen, Fujian, 361005, China. Electronic address:

Phenanthrene (Phe) is a representative polycyclic aromatic hydrocarbon, and its ubiquity makes the risk assessment of Phe in aquatic ecosystems important. To assess the long-term effects of early-life Phe exposure on fish, the embryos of the model organism, zrbrafish (Danio rerio) were exposed to Phe at 0.05, 0.5, 5 and 50 nmol/L for 96 h and then raised to adulthood in clean water. Gonad development and reproductive functions were investigated in 120 day-old fish. The results showed that the percentage of spermatozoa in males and mature oocytes in females were decreased. The spawned egg numbers and the fertilization rate were reduced when the treated fish were mated with untreated fish. The transcription of genes involved in the brain-pituitary-gonadal axis was downregulated. The levels of both 17β-estradiol and testosterone were significantly decreased in the 5 and 50 nmol/L groups compared with the control group. The methylation levels in the promotor of gnrh3 (encoding gonadotropin releasing hormone) were significantly elevated in the adult fish in the 5 and 50 nmol/L treatments, which might be associated with the downregulation of gnrh3 transcription. These results suggested that embryonic exposure to Phe can inhibit the reproductive ability of adult fish, which should be adequately emphasized in its risk assessment.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129635DOI Listing
June 2021

Quantitative Proteomic Profiling of Fungal Growth, Development, and Ochratoxin A Production in on High- and Low-NaCl Cultures.

Toxins (Basel) 2021 01 13;13(1). Epub 2021 Jan 13.

College of Food Science and Technology, Zhejiang University of Technology, Hangzhou 310014, China.

Dry-cured meat products are worldwide food with high-salt content, and filamentous fungi are beneficial to the maturation process. However, some salt-tolerant strains of and produce ochratoxin A (OTA) on these products and thus threaten food safety. In our study, proteomic analysis was performed to reveal the mechanism of adaptability to high-salt environment by . Twenty g/L and 70 g/L NaCl substrates were used to provide medium- and high-NaCl content environments, respectively. The NaCl addition could induce fungal growth, but only 20 g/L NaCl addition could induce spore production while 70 g/L repressed it. Proteomics analysis identified 2646 proteins in fc-1, of which 237 and 251 were differentially expressed with 20 g/L and 70 g/L NaCl addition, respectively. Potential factors affecting fungal growth and development were identified by GO and KEGG analyses of biological process, cellular component, and molecular function terms. The results revealed that ergosterol synthesis pathway was significantly upregulated with 20 g/L and 70 g/L NaCl addition. However, fungal growth and development including OTA production were complex processes associated with many factors including nutrient uptake, cell membrane integrity, cell cycle, energy metabolism, intracellular redox homeostasis, protein synthesis and processing, autophagy, and secondary metabolism. Reactive oxygen species may be an important window to understand the mechanism that medium-salt content was conducive to intracellular signal transduction while high-salt content caused oxidative stress. The findings would help to improve the processes and storage conditions of dry-cured meat products.
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http://dx.doi.org/10.3390/toxins13010051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828334PMC
January 2021

An isocaloric moderately high-fat diet extends lifespan in male rats and Drosophila.

Cell Metab 2021 Mar 12;33(3):581-597.e9. Epub 2021 Jan 12.

National Key Discipline Laboratory, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, P.R. China. Electronic address:

The health effect of dietary fat has been one of the most vexing issues in the field of nutrition. Few animal studies have examined the impact of high-fat diets on lifespan by controlling energy intake. In this study, we found that compared to a normal diet, an isocaloric moderately high-fat diet (IHF) significantly prolonged lifespan by decreasing the profiles of free fatty acids (FFAs) in serum and multiple tissues via downregulating FFA anabolism and upregulating catabolism pathways in rats and flies. Proteomics analysis in rats identified PPRC1 as a key protein that was significantly upregulated by nearly 2-fold by IHF, and among the FFAs, only palmitic acid (PA) was robustly and negatively associated with the expression of PPRC1. Using PPRC1 transgenic RNAi/overexpression flies and in vitro experiments, we demonstrated that IHF significantly reduced PA, which could upregulate PPRC1 through PPARG, resulting in improvements in oxidative stress and inflammation and prolonging the lifespan.
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http://dx.doi.org/10.1016/j.cmet.2020.12.017DOI Listing
March 2021

Initiatives to Scale Up and Expand Reach of Cancer Genomic Services Outside of Specialty Clinical Settings: A Systematic Review.

Am J Prev Med 2021 02 7;60(2):e85-e94. Epub 2020 Nov 7.

Department of Behavioral, Social, and Health Education Sciences, Rollins School of Public Health, Emory University, Atlanta, Georgia.

Context: This systematic review aims to (1) characterize strategies used to identify individuals at increased risk for hereditary breast and ovarian cancer syndrome and Lynch syndrome outside of oncology and clinical genetic settings, (2) describe the extent to which these strategies have extended the reach of genetic services to underserved target populations, and (3) summarize indicators of the potential scalability of these strategies.

Evidence Acquisition: Investigators searched PubMed, EMBASE, and PsycINFO for manuscripts published from October 2005 to August 2019. Eligible manuscripts were those published in English, those that described strategies to identify those at risk for hereditary breast and ovarian cancer syndrome or Lynch syndrome, those implemented outside of an oncology or genetic specialty clinic, and those that included measures of cancer genetic services uptake. This study assessed strategies used to increase the reach of genetic risk screening and counseling services. Each study was evaluated using the 16-item quality assessment tool, and results were reported according to the PRISMA guidelines.

Evidence Synthesis: Of the 16 eligible studies, 11 were conducted in clinical settings and 5 in public health settings. Regardless of setting, most (63%, 10/16) used brief screening tools to identify people with a family history suggestive of hereditary breast and ovarian cancer syndrome or Lynch syndrome. When reported, genetic risk screening reach (range =11%-100%) and genetic counseling reach (range =11%-100%) varied widely across studies. Strategies implemented in public health settings appeared to be more successful (median counseling reach=65%) than those implemented in clinical settings (median counseling reach=26%). Most studies did not describe fundamental components relevant for broad scalability.

Conclusions: Efforts to expand cancer genomic services are limited outside of traditional oncology and genetic clinics. This is a missed opportunity because evidence thus far suggests that these efforts can be successful in expanding the reach of genetic services with the potential to reduce health inequities in access. This review highlights the need for accelerating research that applies evidence-based implementation strategies and frameworks along with process evaluation to understand barriers and facilitators to scalability of strategies with high reach.
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http://dx.doi.org/10.1016/j.amepre.2020.08.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855907PMC
February 2021

Misinterpretation of Hereditary Breast Cancer Risk and Its Association with Information Sharing Motives among Women at Low Likelihood of Carrying a BRCA1/2 Mutation.

Public Health Genomics 2020 27;23(5-6):252-256. Epub 2020 Oct 27.

Department of Behavioral, Social, and Health Education Sciences, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.

Purpose: In this brief report, we ask whether women's interpretation of breast cancer risk based on their low likelihood of carrying a BRCA1/2 mutation is associated with their information-sharing behavior, and whether misinterpretation is associated with motives for sharing the result.

Methods: Women in mammography clinics who completed a brief family history assessment and deemed to be at low likelihood of carrying a BRCA1/2 mutation were asked to complete a 1-time online survey between June 2016 and January 2017.

Results: One-third (44/148) of women shared their family history screen result with someone in their social network. Result information was shared largely with a first-degree female relative to express feelings of relief (77%, 33/43). There were no differences in likelihood of sharing based on breast cancer risk interpretation. However, women who misinterpreted the implications of the result for general breast cancer risk reported more motives to share the result with their social network than those who accurately interpreted their breast cancer risk.

Conclusions: As family history-based screening for hereditary breast cancer is broadly implemented, the communication needs of the majority of women who will be unlikely of carrying a BRCA1/2 mutation must be considered. The motives of women who misinterpreted the implications of this result for breast cancer risk suggest the possibility that miscommunication could be spread to the broader family network.
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http://dx.doi.org/10.1159/000511131DOI Listing
May 2021

Tunable Electronic Properties of Type-II SiS/WSe Hetero-Bilayers.

Nanomaterials (Basel) 2020 Oct 15;10(10). Epub 2020 Oct 15.

College of Science, University of Shanghai for Science and Technology, Shanghai 200093, China.

First-principle calculations based on the density functional theory (DFT) are implemented to study the structural and electronic properties of the SiS/WSe hetero-bilayers. It is found that the AB-2 stacking model is most stable among all the six SiS/WSe heterostructures considered in this work. The AB-2 stacking SiS/WSe hetero-bilayer possesses a type-II band alignment with a narrow indirect band gap (0.154 eV and 0.738 eV obtained by GGA-PBE and HSE06, respectively), which can effectively separate the photogenerated electron-hole pairs and prevent the recombination of the electron-hole pairs. Our results revealed that the band gap can be tuned effectively within the range of elastic deformation (biaxial strain range from -7% to 7%) while maintaining the type-II band alignment. Furthermore, due to the effective regulation of interlayer charge transfer, the band gap along with the band offset of the SiS/WSe heterostructure can also be modulated effectively by applying a vertical external electric field. Our results offer interesting alternatives for the engineering of two-dimensional material-based optoelectronic nanodevices.
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http://dx.doi.org/10.3390/nano10102037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602600PMC
October 2020

Integrated analysis of immune-related genes in endometrial carcinoma.

Cancer Cell Int 2020 2;20:477. Epub 2020 Oct 2.

The Department of Radiotherapy Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang China.

Background: Exploring novel and sensitive targets is urgent due to the high morbidity of endometrial cancer (EC). The purpose of our study was to explore the transcription factors and immune-related genes in EC and further identify immune-based lncRNA signature as biomarker for predicting survival prognosis.

Methods: Transcription factors, aberrantly expressed immune-related genes and immune-related lncRNAs were explored through bioinformatics analysis. Cox regression and the least absolute shrinkage and selection operator (LASSO) analysis were conducted to identify the immune and overall survival (OS) related lncRNAs. The accuracy of model was evaluated by Kaplan-Meier method and receiver operating characteristic (ROC) analysis, and the independent prognostic indicator was identified with Cox analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to detect the accuracy of our results.

Results: A network of 29 transcription factors and 17 immune-related genes was constructed. Furthermore, four immune-prognosis-related lncRNAs were screened out. Kaplan-Meier survival analysis and time-dependent ROC analysis revealed a satisfactory predictive potential of the 4-lncRNA model. Consistency was achieved among the results from the training set, testing set and entire cohort. The distributed patterns between the high- and low-risk groups could be distinguished in principal component analysis. Comparisons of the risk score and clinical factors confirmed the four-lncRNA-based signature as an independent prognostic indicator. Last, the reliability of the results was verified by qRT-PCR in 29 cases of endometrial carcinoma and in cells.

Conclusions: Overall, our study constructed a network of transcription factors and immune-related genes and explored a four immune-related lncRNA signature that could serve as a novel potential biomarker of EC.
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http://dx.doi.org/10.1186/s12935-020-01572-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531161PMC
October 2020

Accelerating T mapping of the brain by integrating deep learning priors with low-rank and sparse modeling.

Magn Reson Med 2021 03 29;85(3):1455-1467. Epub 2020 Sep 29.

Beckman Institute of Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.

Purpose: To accelerate T mapping with highly sparse sampling by integrating deep learning image priors with low-rank and sparse modeling.

Methods: The proposed method achieves high-speed T mapping by highly sparsely sampling (k, TE)-space. Image reconstruction from the undersampled data was done by exploiting the low-rank structure and sparsity in the T -weighted image sequence and image priors learned from training data. The image priors for a single TE were generated from the public Human Connectome Project data using a tissue-based deep learning method; the image priors were then transferred to other TEs using a generalized series-based method. With these image priors, the proposed reconstruction method used a low-rank model and a sparse model to capture subject-dependent novel features.

Results: The proposed method was evaluated using experimental data obtained from both healthy subjects and tumor patients using a turbo spin-echo sequence. High-quality T maps at the resolution of 0.9 × 0.9 × 3.0 mm were obtained successfully from highly undersampled data with an acceleration factor of 8. Compared with the existing compressed sensing-based methods, the proposed method produced significantly reduced reconstruction errors. Compared with the deep learning-based methods, the proposed method recovered novel features better.

Conclusion: This paper demonstrates the feasibility of learning T -weighted image priors for multiple TEs using tissue-based deep learning and generalized series-based learning. A new method was proposed to effectively integrate these image priors with low-rank and sparse modeling to reconstruct high-quality images from highly undersampled data. The proposed method will supplement other acquisition-based methods to achieve high-speed T mapping.
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http://dx.doi.org/10.1002/mrm.28526DOI Listing
March 2021

Skeleton optimization of neuronal morphology based on three-dimensional shape restrictions.

BMC Bioinformatics 2020 Sep 4;21(1):395. Epub 2020 Sep 4.

Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, MoE Key Laboratory for Biomedical Photonics, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, China.

Background: Neurons are the basic structural unit of the brain, and their morphology is a key determinant of their classification. The morphology of a neuronal circuit is a fundamental component in neuron modeling. Recently, single-neuron morphologies of the whole brain have been used in many studies. The correctness and completeness of semimanually traced neuronal morphology are credible. However, there are some inaccuracies in semimanual tracing results. The distance between consecutive nodes marked by humans is very long, spanning multiple voxels. On the other hand, the nodes are marked around the centerline of the neuronal fiber, not on the centerline. Although these inaccuracies do not seriously affect the projection patterns that these studies focus on, they reduce the accuracy of the traced neuronal skeletons. These small inaccuracies will introduce deviations into subsequent studies that are based on neuronal morphology files.

Results: We propose a neuronal digital skeleton optimization method to evaluate and make fine adjustments to a digital skeleton after neuron tracing. Provided that the neuronal fiber shape is smooth and continuous, we describe its physical properties according to two shape restrictions. One restriction is designed based on the grayscale image, and the other is designed based on geometry. These two restrictions are designed to finely adjust the digital skeleton points to the neuronal fiber centerline. With this method, we design the three-dimensional shape restriction workflow of neuronal skeleton adjustment computation. The performance of the proposed method has been quantitatively evaluated using synthetic and real neuronal image data. The results show that our method can reduce the difference between the traced neuronal skeleton and the centerline of the neuronal fiber. Furthermore, morphology metrics such as the neuronal fiber length and radius become more precise.

Conclusions: This method can improve the accuracy of a neuronal digital skeleton based on traced results. The greater the accuracy of the digital skeletons that are acquired, the more precise the neuronal morphologies that are analyzed will be.
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http://dx.doi.org/10.1186/s12859-020-03714-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472589PMC
September 2020

Evaluation on Elongation Factor 1 Alpha of Interaction with the Intermediate Subunit of the Gal/GalNAc Lectin and Actin in Phagocytosis.

Pathogens 2020 Aug 27;9(9). Epub 2020 Aug 27.

Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.

is the causative agent of amoebiasis. This disease results in 40,000 to 100,000 deaths annually. The pathogenic molecules involved in the invasion of trophozoites had been constantly being clarified. This study explored the role of elongation factor 1 alpha (EF1a) in pathogenicity. Biolayer interferometry binding and pull-down assays suggest that EF1a and intermediate subunit of lectin (Igl) binding are specific. Submembranous distribution of EF1a closely aligns with the localization of Igl, which appear in abundance on membranes of trophozoites. Messenger RNA (mRNA) expression of EF1a is positively correlated with trends in Igl levels after co-incubation with Chinese hamster ovary (CHO) cells in vitro, suggesting a regulatory linkage between these proteins. Erythrophagocytosis assays also imply a role for EF1a in phagocytosis. Finally, EF1a and actin are collocated in trophozoites. These results indicated elongation factor 1a is associated with phagocytosis, and the relationships between EF1a, Igl, and actin are worth further study to better understand the pathogenic process.
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http://dx.doi.org/10.3390/pathogens9090702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558290PMC
August 2020

DeepMapi: a Fully Automatic Registration Method for Mesoscopic Optical Brain Images Using Convolutional Neural Networks.

Neuroinformatics 2021 04;19(2):267-284

Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, MoE Key Laboratory for Biomedical Photonics, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, China.

The extreme complexity of mammalian brains requires a comprehensive deconstruction of neuroanatomical structures. Scientists normally use a brain stereotactic atlas to determine the locations of neurons and neuronal circuits. However, different brain images are normally not naturally aligned even when they are imaged with the same setup, let alone under the differing resolutions and dataset sizes used in mesoscopic imaging. As a result, it is difficult to achieve high-throughput automatic registration without manual intervention. Here, we propose a deep learning-based registration method called DeepMapi to predict a deformation field used to register mesoscopic optical images to an atlas. We use a self-feedback strategy to address the problem of imbalanced training sets (sampling at a fixed step size in nonuniform brains of structures and deformations) and use a dual-hierarchical network to capture the large and small deformations. By comparing DeepMapi with other registration methods, we demonstrate its superiority over a set of ground truth images, including both optical and MRI images. DeepMapi achieves fully automatic registration of mesoscopic micro-optical images, even macroscopic MRI datasets, in minutes, with an accuracy comparable to those of manual annotations by anatomists.
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http://dx.doi.org/10.1007/s12021-020-09483-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004526PMC
April 2021

The phytochemical epigallocatechin gallate prolongs the lifespan by improving lipid metabolism, reducing inflammation and oxidative stress in high-fat diet-fed obese rats.

Aging Cell 2020 09 30;19(9):e13199. Epub 2020 Jul 30.

Department of Nutrition and Food Hygiene, College of Public Health, Harbin Medical University, Harbin, Heilongjiang, China.

We have recently reported that epigallocatechin gallate (EGCG) could extend lifespan in healthy rats. This study aimed to investigate the effects and mechanisms of a high dose of EGCG in extending the lifespan of obese rats. Ninety adult male Wistar rats were randomly divided into the control (NC), high-fat (HF) and EGCG groups. Serum glucose and lipids, inflammation and oxidative stress were dynamically determined from adulthood to death, and the transcriptome and proteome of the liver were also examined. The median lifespans of the NC, HF and EGCG groups were 693, 599 and 683 days, respectively, and EGCG delayed death by 84 days in obese rats. EGCG improved serum glucose and lipids and reduced inflammation and oxidative stress associated with aging in obese rats induced by a high-fat diet. EGCG also significantly decreased the levels of total free fatty acids (FFAs), SFAs and the n-6/n-3 ratio but significantly increased the n-3 FFAs related to longevity. The joint study of the transcriptome and proteome in liver found that EGCG exerted its effects mainly by regulating the suppression of hydrogen peroxide and oxygen species metabolism, suppression of oxidative stress, activation of fatty acid transport and oxidation and cholesterol metabolism. EGCG significantly increased the protein expression of FOXO1, Sirt1, CAT, FABP1, GSTA2, ACSL1 and CPT2 but significantly decreased NF-κB, ACC1 and FAS protein levels in the livers of rats. All the results indicate that EGCG extends lifespan by improving FFA metabolism and reducing the levels of inflammatory and oxidative stress in obese rats.
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http://dx.doi.org/10.1111/acel.13199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511879PMC
September 2020

Association between small intestinal bacterial overgrowth and beta-cell function of type 2 diabetes.

J Int Med Res 2020 Jul;48(7):300060520937866

NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin, China.

Aims: Previous studies suggest that small intestinal bacterial overgrowth (SIBO) is associated with type 2 diabetes. However, few studies have evaluated the association between SIBO and beta-cell function in type 2 diabetes. The aim of this study was to evaluate whether beta-cell function was associated with SIBO.

Materials And Methods: One hundred four patients with type 2 diabetes were included in this study. Based on the presence of SIBO, the patients were divided into SIBO-positive and SIBO-negative groups. Oral glucose tolerance tests were performed. Insulin sensitivity was measured using 1/homeostasis model assessment of insulin resistance (1/HOMA-IR) and the insulin sensitivity index (ISIM). Insulin release was calculated by HOMA-β, early-phase insulin secretion index InsAUC/GluAUC, and total-phase insulin secretion index InsAUC/GluAUC.

Results: Compared with the SIBO-negative group, patients in the SIBO-positive group showed a higher glucose level at 120 minutes, HbA1c, 1/HOMA-IR, and ISIM and a lower HOMA-β level, early-phase InsAUC/GluAUC, and total-phase InsAUC/GluAUC. Multiple linear regression analysis showed that body mass index, glucose at 0 minutes, and SIBO were independently associated with the early-phase and total-phase insulin secretion.

Conclusion: SIBO may be involved in lower levels of insulin release and worse glycemic control.
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http://dx.doi.org/10.1177/0300060520937866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375730PMC
July 2020

Role of bone marrow-derived mesenchymal stem cell defects in CD8 CD28 suppressor T-lymphocyte induction in patients with immune thrombocytopenia and associated mechanisms.

Br J Haematol 2020 12 16;191(5):852-862. Epub 2020 Jul 16.

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China.

Many immune dysfunctions participate in immune thrombocytopenia (ITP) pathogenesis, including numeric and functional defects in suppressor T (Ts) cells and immune-regulation abnormalities in mesenchymal stem cells (MSCs). Recent studies showed that MSCs can promote Ts cell differentiation. Thus, we compared the Ts cell induction ability of bone marrow-derived MSCs (BM-MSCs) between patients with ITP and normal controls (NCs), and examined the mechanism of this difference. Co-culture of CD8 T cells with BM-MSCs revealed that BM-MSCs elevated Ts cell percentage and function, but the efficiency was lower in patients with ITP than in NCs. Blockade experiments showed that blockade of interleukin 6 (IL-6) partially reversed Ts cell induction by BM-MSCs. Addition of exogenous IL-6 down-regulated Ts cell apoptosis. Moreover, BM-MSCs enhanced IL-10 secretion and inhibition ability of Ts cells. IL-6 secretion, regulatory abilities of IL-10 expression in Ts cells, and the enhanced efficiency of Ts cells inhibition function by BM-MSCs were all decreased in patients with ITP. All-trans retinoic acid preconditioning promoted BM-MSC induction of Ts cell percentages and umbilical cord-derived (UC) MSCs efficiently improved ITP Ts cell numbers and dysfunction. In conclusion, defects of BM-MSCs in Ts cell induction are involved in ITP pathogenesis, and exogenous UC-MSCs may be useful for ITP therapy.
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http://dx.doi.org/10.1111/bjh.16953DOI Listing
December 2020

Renal cell tumors convert natural killer cells to a proangiogenic phenotype.

Oncotarget 2020 Jun 30;11(26):2571-2585. Epub 2020 Jun 30.

Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA.

Natural killer (NK) cells are classically associated with immune surveillance and destruction of tumor cells. Inconsistent with this function, NK cells are found in advanced human tumors including renal cell carcinoma (RCC). NK cells with non-classical phenotypes (CD56CD16; termed decidua NK (dNK) cells) accumulate at the maternal-fetal interface during embryo implantation. These dNK cells are poorly cytotoxic, proangiogenic, and facilitate placenta development. As similarities between embryo implantation and tumor growth exist, we tested the hypothesis that an analogous shift in NK cell phenotype and function occurs in RCC tumors. Our results show that peripheral NK (pNK) cells of RCC patients were uniformly CD56CD16, but lacked full cytotoxic ability. By comparison, RCC tumor-infiltrated NK (TiNK) cells were significantly enriched for CD56CD16 cells, a phenotype of dNK cells. Gene expression analysis revealed that angiogenic and inflammatory genes were significantly increased for RCC TiNK versus RCC pNK populations, with enrichment of genes in the hypoxia inducible factor (HIF) 1α pathway. Consistent with this finding, NK cells cultured under hypoxia demonstrated limited cytotoxicity capacity, but augmented production of vascular endothelial growth factor (VEGF). Finally, comparison of gene expression data for RCC TiNK and dNK cells revealed a shared transcriptional signature of genes with known roles in angiogenesis and immunosuppression. These studies confirm conversion of pNK cells to a dNK-like phenotype in RCC tumors. These characteristics are conceivably beneficial for placentation, but likely exploited to support early tumor growth and promote metastasis.
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http://dx.doi.org/10.18632/oncotarget.27654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335666PMC
June 2020

Anatomically revealed morphological patterns of pyramidal neurons in layer 5 of the motor cortex.

Sci Rep 2020 05 13;10(1):7916. Epub 2020 May 13.

Britton Chance Center for Biomedical Photonics, Key Laboratory for Biomedical Photonics of Ministry of Education, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, 430074, China.

Neuronal cell types are essential to the comprehensive understanding of the neuronal function and neuron can be categorized by their anatomical property. However, complete morphology data for neurons with a whole brain projection, for example the pyramidal neurons in the cortex, are sparse because it is difficult to trace the neuronal fibers across the whole brain and acquire the neuron morphology at the single axon resolution. Thus the cell types of pyramidal neurons have yet to be studied at the single axon resolution thoroughly. In this work, we acquire images for a Thy1 H-line mouse brain using a fluorescence micro-optical sectioning tomography system. Then we sample 42 pyramidal neurons whose somata are in the layer 5 of the motor cortex and reconstruct their morphology across the whole brain. Based on the reconstructed neuronal anatomy, we analyze the axonal and dendritic fibers of the neurons in addition to the soma spatial distributions, and identify two axonal projection pattern of pyramidal tract neurons and two dendritic spreading patterns of intratelencephalic neurons. The raw image data are available upon request as an additional asset to the community. The morphological patterns identified in this work can be a typical representation of neuron subtypes and reveal the possible input-output function of a single pyramidal neuron.
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http://dx.doi.org/10.1038/s41598-020-64665-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220918PMC
May 2020

FOLFOX Chemotherapy Ameliorates CD8 T Lymphocyte Exhaustion and Enhances Checkpoint Blockade Efficacy in Colorectal Cancer.

Front Oncol 2020 23;10:586. Epub 2020 Apr 23.

Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO, United States.

Colorectal cancer (CRC) is the third most common malignancy worldwide. The presence of CD8 tumor-infiltrating T lymphocytes (TILs) is associated with improved prognosis and therapeutic response in CRC patients. FOLFOX chemotherapy is a standard first-line treatment for patients with CRC. Yet, the effect of FOLFOX on TILs is poorly understood. Specifically, it is unclear whether FOLFOX therapy impacts the phenotype and functionality of tumor antigen specific TILs. Immune checkpoint blockade (ICB) has significantly improved clinical outcome of cancer treatment but has shown limited efficacy in CRC patients. Recently, ICB efficiency has been linked to reinvigoration of T cells with a non-terminally dysfunctional phenotype. Here, we investigate the effect of FOLFOX on CD8 T cell tumor accumulation, phenotype and function and tested the combination of FOLFOX and ICB to improve tumor regression. A mouse model of CRC expressing a human tumor antigen was used to study the effect of FOLFOX on tumor growth and TILs phenotype and function. Tetramers were used to identify and monitor phenotype and function of tumor specific TILs. The phenotype and function of TILs were compared between FOLFOX and control treatment through flow cytometry, depletion and stimulation. Furthermore, the anti-tumor effect of the single drug or combined therapy with anti-PD1 were also assessed. We show that FOLFOX treatment effectively controlled tumor burden and this was dependent on CD8 T cells. FOLFOX enabled TILs to remain in a functional differentiation state characterized by lower levels of inhibitory receptors PD-1 and TIM-3 and a CD38CD101TIM-3TCF-1 phenotype. Consistent with this, TILs from FOLFOX treated tumors exhibited higher effector function. Importantly, while anti-PD-1 treatment alone had no significant effect on tumor burden, FOLFOX and PD-1 checkpoint blockade combination showed significant tumor control. FOLFOX treatment impacts the phenotype and function of TILs making them more responsive to checkpoint blockade. This study highlights the importance of combining chemotherapy and ICB to optimize treatment efficacy in patients with colorectal cancer.
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http://dx.doi.org/10.3389/fonc.2020.00586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190812PMC
April 2020

DeepBrainSeg: Automated Brain Region Segmentation for Micro-Optical Images With a Convolutional Neural Network.

Front Neurosci 2020 20;14:179. Epub 2020 Mar 20.

Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, China.

The segmentation of brain region contours in three dimensions is critical for the analysis of different brain structures, and advanced approaches are emerging continuously within the field of neurosciences. With the development of high-resolution micro-optical imaging, whole-brain images can be acquired at the cellular level. However, brain regions in microscopic images are aggregated by discrete neurons with blurry boundaries, the complex and variable features of brain regions make it challenging to accurately segment brain regions. Manual segmentation is a reliable method, but is unrealistic to apply on a large scale. Here, we propose an automated brain region segmentation framework, DeepBrainSeg, which is inspired by the principle of manual segmentation. DeepBrainSeg incorporates three feature levels to learn local and contextual features in different receptive fields through a dual-pathway convolutional neural network (CNN), and to provide global features of localization by image registration and domain-condition constraints. Validated on biological datasets, DeepBrainSeg can not only effectively segment brain-wide regions with high accuracy (Dice ratio > 0.9), but can also be applied to various types of datasets and to datasets with noises. It has the potential to automatically locate information in the brain space on the large scale.
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http://dx.doi.org/10.3389/fnins.2020.00179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099146PMC
March 2020

Genetic counseling education at the undergraduate level: An outreach initiative to promote professional recruitment and support workforce development.

J Genet Couns 2020 04 30;29(2):234-242. Epub 2020 Mar 30.

Department of Genetic Engineering, SRM University, Chennai, India.

As in many other countries, the field of genetic counseling is in its initial stages of development in India, where there are efforts to streamline the profession and to implement graduate-level training programs. We implemented an elective course on genetic counseling at the undergraduate level in a private university in India to assess students' interest, to provide early exposure for students interested in pursuing the career, and to aid recruitment. To assess satisfaction with the course and recruitment outcomes, we sent a course evaluation survey to 332 students and received 134 responses. Familiarity with genetic counseling topics increased significantly after completing the course. Of the 42 respondents who reported they were planning to pursue formal genetic counseling training, 21% (n = 9/42) became interested in the profession as a result of taking this course. Survey respondents who were prospective applicants to genetic counseling training programs referred mostly to the websites of the National Society of Genetic Counselors and the American Board of Genetic Counseling for information on genetic counseling and training. Barriers to entry into the field included lack of shadowing opportunities, inadequate coursework, and limited opportunities to interact with practicing genetic counselors. Respondents stated that additional case studies as well as observation of patient interactions would elucidate the role of a genetic counselor and help define the scope of the practice in India and other countries. Overall, genetic counseling education at the undergraduate level is a scalable way to improve understanding of genetic counseling topics, increase professional interest in the field, and support workforce development.
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http://dx.doi.org/10.1002/jgc4.1253DOI Listing
April 2020

Renal protection of rhein against 5/6 nephrectomied-induced chronic kidney disease: role of SIRT3-FOXO3α signalling pathway.

J Pharm Pharmacol 2020 May 20;72(5):699-708. Epub 2020 Mar 20.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Objectives: The purpose of this study is to investigate the antifibrosis and anti-oxidation of rhein in vivo and in vitro, and to evaluate potential mechanisms involved in the treatment of chronic kidney disease (CKD).

Methods: In experimental animal studies, CKD was established by 5/6 nephrectomy (5/6Nx). Serum creatinine (Scr) and blood urea nitrogen (BUN) were determined. Histopathologic tests were performed by HE and Masson trichrome stained. The level of ROS was investigated by fluorescence microplate with the probe 2', 7'-dichlorofluorescein diacetate (DCFH-DA). The protein expressions of p47phox and gp91phox were measured in 5/6Nx rats. In HK-2 cells, the expression of SIRT3 and Foxo3α was measured in SIRT3 knockdown conditions. The indicators of oxidation and fibrosisi were measured in SIRT3 knockdown conditions.

Key Findings: The results showed that, in addition to reducing renal interstitial pathologic injury and collagen fibrils, rhein administration improved renal function. The protective mechanisms were attributed to active SIRT3/FOXO3α signalling pathway and then play the anti-oxidative capacity of rhein, as well as to subsequent antifibrotic effect.

Conclusion: Taken together, rhein protected kidney through SIRT3/FOXO3a involvement. The anti-oxidative capacity of rhein contributed to the protective effects including the subsequent antifibrotic responses.
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http://dx.doi.org/10.1111/jphp.13234DOI Listing
May 2020

Patient perspectives on the diagnostic journey to a monogenic diabetes diagnosis: Barriers and facilitators.

J Genet Couns 2020 12 12;29(6):1106-1113. Epub 2020 Mar 12.

Division of Endocrinology, Diabetes & Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.

Most monogenic diabetes is misdiagnosed as either type 1 or type 2 diabetes (T1D/T2D). Few studies have examined the diagnostic challenges from the patients' perspective. This qualitative study aimed to investigate patients' journeys to obtaining a diagnosis of maturity-onset diabetes of the young (MODY) by elucidating the range of factors that can act as barriers and facilitators throughout this process. We recruited participants from the Personalized Diabetes Medicine Program (PDMP) at University of Maryland and used respondent-driven sampling to recruit additional patients. We conducted qualitative phone interviews between October 2016 and June 2017 with nine patients with diagnoses of monogenic diabetes (one HNF4A-MODY, seven GCK-MODY, and one HNF1A-MODY) and one parent of a patient with INS-MODY. Interview data were audio recorded, transcribed, and analyzed both inductively and deductively using thematic content analysis. All patients were female, with a mean age of 35 (range: 7-67 years). The amount of time these patients were misdiagnosed ranged from a few months to 41 years. We identified barriers and facilitators in three broad themes: (a) patient-related (nature of MODY symptoms, perceived test utility, individual personality); (b) provider-related (provider awareness and knowledge, provider communication); and (c) healthcare system-related (cost of testing, access to knowledgeable providers, patient education, and support resources). The diverse range of barriers and facilitators reiterates the complexity of the MODY diagnostic process. Limited awareness and knowledge of MODY from healthcare professionals and patients themselves account for most diagnostic delays described in this study. Efforts to promote awareness of MODY and expand access to screening and testing may result in quicker diagnosis and ensure the downstream benefits of proper treatment.
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http://dx.doi.org/10.1002/jgc4.1247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486254PMC
December 2020

Immunogenomic pathways associated with cytotoxic lymphocyte infiltration and survival in colorectal cancer.

BMC Cancer 2020 Feb 14;20(1):124. Epub 2020 Feb 14.

Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA.

Background: Colorectal cancer (CRC) is the second leading cancer killer in the US today and patients with metastatic disease have only a 14% 5-year survival. One of the most impactful recent advances in cancer therapy, immune checkpoint inhibition, has not been shown to be effective for the majority of these patients. In this study, we use The Cancer Genome Atlas (TCGA) and recently developed informatic-based tools to identify targets for immune based therapy in colorectal cancer patients.

Methods: Open access, pre-processed (level 3) mRNA data and clinical data from colorectal patients from the TCGA was downloaded from FireCloud. Using the Microenvironment Cell Populations-Counter method (MCP-Counter), cytotoxic lymphocyte scores were calculated for all patients. Patients were then grouped by cytotoxic lymphocyte score (High vs Low), pathologic stage, and location to identify differentially expressed genes. Pathway enrichment analysis was performed using Reactome to determine differentially expressed genes associated with immune pathways. Survival analysis was performed with identified differentially expressed genes.

Results: In the TCGA dataset, there are 461 colon and 172 rectal cancer patients. After stratifying patients by cytotoxic lymphocyte score, anatomical location, and stage, we found a significant number of differentially expressed genes. We identified one pathway, "immunoregulatory interactions between a lymphoid and non-lymphoid cell", that was highly enriched and included in all tumor locations and stages. Survival analysis performed with differentially expressed genes in this pathway identified 21 different genes associated with survival and cytotoxic lymphocyte infiltration, with ~ 70% of these genes occurring in the metastatic right-sided CRC group. Specifically, all genes associated with survival in the metastatic right-sided colorectal cancer group with low cytotoxic lymphocyte scores positively impacted survival.

Conclusions: Utilizing the TCGA, a publicly available dataset, and informatics-based analyses, we identified potential targets to improve immune based therapy in colorectal cancer. Additionally, we note the most targets in metastatic right-sided CRC patients, the patient group with the worst predicted survival. The results from this study demonstrate the ability of informatics-based analytic techniques to identify new therapeutic targets as well as improve patient selection for intervention, helping us to achieve the goals of precision-based oncology.
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http://dx.doi.org/10.1186/s12885-020-6513-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023815PMC
February 2020

A Robust Image Registration Interface for Large Volume Brain Atlas.

Sci Rep 2020 02 7;10(1):2139. Epub 2020 Feb 7.

Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, China.

Accurately mapping brain structures in three-dimensions is critical for an in-depth understanding of brain functions. Using the brain atlas as a hub, mapping detected datasets into a standard brain space enables efficient use of various datasets. However, because of the heterogeneous and nonuniform brain structure characteristics at the cellular level introduced by recently developed high-resolution whole-brain microscopy techniques, it is difficult to apply a single standard to robust registration of various large-volume datasets. In this study, we propose a robust Brain Spatial Mapping Interface (BrainsMapi) to address the registration of large-volume datasets by introducing extracted anatomically invariant regional features and a large-volume data transformation method. By performing validation on model data and biological images, BrainsMapi achieves accurate registration on intramodal, individual, and multimodality datasets and can also complete the registration of large-volume datasets (approximately 20 TB) within 1 day. In addition, it can register and integrate unregistered vectorized datasets into a common brain space. BrainsMapi will facilitate the comparison, reuse and integration of a variety of brain datasets.
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http://dx.doi.org/10.1038/s41598-020-59042-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005806PMC
February 2020