Publications by authors named "Chao Huang"

921 Publications

Systems pharmacology: a combination strategy for improving efficacy of PD-1/PD-L1 blockade.

Brief Bioinform 2021 Apr 20. Epub 2021 Apr 20.

Center of Bioinformatics, College of Life Sciences, Northwest A&F University and at Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, School of Life Sciences, Northwest University, China.

Targeting tumor microenvironment (TME), such as immune checkpoint blockade (ICB), has achieved increased overall response rates in many advanced cancers, such as non-small cell lung cancer (NSCLC), however, only in a fraction of patients. To improve the overall and durable response rates, combining other therapeutics, such as natural products, with ICB therapy is under investigation. Unfortunately, due to the lack of systematic methods to characterize the relationship between TME and ICB, development of rational immune-combination therapy is a critical challenge. Here, we proposed a systems pharmacology strategy to identify resistance regulators of PD-1/PD-L1 blockade and develop its combinatorial drug by integrating multidimensional omics and pharmacological methods. First, a high-resolution TME cell atlas was inferred from bulk sequencing data by referring to a high-resolution single-cell data and was used to predict potential resistance regulators of PD-1/PD-L1 blockade through TME stratification analysis. Second, to explore the drug targeting the resistance regulator, we carried out the large-scale target fishing and the network analysis between multi-target drug and the resistance regulator. Finally, we predicted and verified that oxymatrine significantly enhances the infiltration of CD8+ T cells into TME and is a powerful combination agent to enhance the therapeutic effect of anti-PD-L1 in a mouse model of lung adenocarcinoma. Overall, the systems pharmacology strategy offers a paradigm to identify combinatorial drugs for ICB therapy with a systems biology perspective of drug-target-pathway-TME phenotype-ICB combination.
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http://dx.doi.org/10.1093/bib/bbab130DOI Listing
April 2021

CircLIFR synergizes with MSH2 to attenuate chemoresistance via MutSα/ATM-p73 axis in bladder cancer.

Mol Cancer 2021 Apr 19;20(1):70. Epub 2021 Apr 19.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: Cisplatin (CDDP) has become a standard-of-care treatment for muscle-invasive bladder cancer (MIBC), while chemoresistance remains a major challenge. Accumulating evidence indicates that circular RNAs (circRNAs) are discrete functional entities. However, the regulatory functions as well as complexities of circRNAs in modulating CDDP-based chemotherapy in bladder cancer are yet to be well revealed.

Methods: Through analyzing the expression profile of circRNAs in bladder cancer tissues, RNA FISH, circRNA pull-down assay, mass spectrometry analysis and RIP, circLIFR was identified and its interaction with MSH2 was confirmed. The effects of circLIFR and MSH2 on CDDP-based chemotherapy were explored by flow cytometry and rescue experiments. Co-IP and Western blot were used to investigate the molecular mechanisms underlying the functions of circLIFR and MSH2. Biological implications of circLIFR and MSH2 in bladder cancer were implemented in tumor xenograft models and PDX models.

Results: CircLIFR was downregulated in bladder cancer and expression was positively correlated with favorable prognosis. Moreover, circLIFR synergizing with MSH2, which was a mediator of CDDP sensitivity in bladder cancer cells, positively modulated sensitivity to CDDP in vitro and in vivo. Mechanistically, circLIFR augmented the interaction between MutSα and ATM, ultimately contributing to stabilize p73, which triggered to apoptosis. Importantly, MIBC with high expression of circLIFR and MSH2 was more sensitive to CDDP-based chemotherapy in tumor xenograft models and PDX models.

Conclusions: CircLIFR could interact with MSH2 to positively modulate CDDP-sensitivity through MutSα/ATM-p73 axis in bladder cancer. CircLIFR and MSH2 might be act as promising therapeutic targets for CDDP-resistant bladder cancer.
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http://dx.doi.org/10.1186/s12943-021-01360-4DOI Listing
April 2021

Carbon and nitrogen isotopic compositions of particulate organic matter in the upwelling zone off the east coast of Hainan Island, China.

Mar Pollut Bull 2021 Apr 14;167:112349. Epub 2021 Apr 14.

College of Ocean and Meteorology, Guangdong Ocean University, Zhanjiang 524088, China.

The isotopic compositions (δC and δN) and C/N ratios of suspended particulate organic matter (POM) were investigated off the east coast of Hainan Island in the South China Sea during summer. Coastal upwelling influenced the nearshore stations of transects S2 and S3, and higher δC and δN values suggested that coastal upwelling played a significant role in determining the POM sources. The POM at the nearshore area of transect S1 was controlled by the coastal current and freshwater discharge. Additionally, organic matter may be transported to the offshore area via tidal movements in transects S1 and S3. Based on the stable isotope analysis in an R model, the marine organic matter contribution in the upwelling area (19%) was higher than that in the other areas (transect S1 and the offshore area) (7%). The δC and δN values and C/N ratios reflect the carbon and nitrogen sources and their cycling in the upwelling zone off the east coast of Hainan Island.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112349DOI Listing
April 2021

New pectic polysaccharides from Codonopsis pilosula and C. tangshen: structural characterization and cellular antioxidant activities.

J Sci Food Agric 2021 Apr 15. Epub 2021 Apr 15.

Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China.

Background: Codonopsis pilosula and C. tangshen are plants widely used in traditional Chinese medicine. Two pectic polysaccharides from roots of C. pilosula and C. tangshen named as CPP-1 and CTP-1 were obtained by boiling water extraction and column chromatography.

Results: The core structure of both CPP-1 and CTP-1 are long homogalacturonan regions (HG) region as the backbone, and the rhamnogalacturonan I (RG-I) region as the side chains. While CPP-1 has the methyl esterified galacturonic acid units and slightly lower molecular weight than CTP-1. The biological test suggested that CPP-1 and CTP-1 can protect IPEC-J2 cells against the H O -induced oxidative stress via up-regulating Nrf2 and related genes in IPEC-J2 cells. The different antioxidative activities of polysaccharides from different source of C. pilosula may be result of the difference in their structures.

Conclusion: All results indicated that pectic polysaccharides CPP-1 and CTP-1 from different species of C. pilosula roots could be used as a potential natural antioxidant source. These findings will be valuable for further studies and new applications of pectin-containing health products. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jsfa.11261DOI Listing
April 2021

CircPTPRA blocks the recognition of RNA N-methyladenosine through interacting with IGF2BP1 to suppress bladder cancer progression.

Mol Cancer 2021 Apr 14;20(1):68. Epub 2021 Apr 14.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: Circular RNAs (circRNAs) have been found to have significant impacts on bladder cancer (BC) progression through various mechanisms. In this study, we aimed to identify novel circRNAs that regulate the function of IGF2BP1, a key mA reader, and explore the regulatory mechanisms and clinical significances in BC.

Methods: Firstly, the clinical role of IGF2BP1 in BC was studied. Then, RNA immunoprecipitation sequencing (RIP-seq) analysis was performed to identify the circRNAs interacted with IGF2BP1 in BC cells. The overall biological roles of IGF2BP1 and the candidate circPTPRA were investigated in both BC cell lines and animal xenograft studies. Subsequently, we evaluated the regulation effects of circPTPRA on IGF2BP1 and screened out its target genes through RNA sequencing. Finally, we explored the underlying molecular mechanisms that circPTPRA might act as a blocker in recognition of mA.

Results: We demonstrated that IGF2BP1 was predominantly binded with circPTPRA in the cytoplasm in BC cells. Ectopic expression of circPTPRA abolished the promotion of cell proliferation, migration and invasion of BC cells induced by IGF2BP1. Importantly, circPTPRA downregulated IGF2BP1-regulation of MYC and FSCN1 expression via interacting with IGF2BP1. Moreover, the recognition of mA-modified RNAs mediated by IGF2BP1 was partly disturbed by circPTPRA through its interaction with KH domains of IGF2BP1.

Conclusions: This study identifies exonic circular circPTPRA as a new tumor suppressor that inhibits cancer progression through endogenous blocking the recognition of IGF2BP1 to mA-modified RNAs, indicating that circPTPRA may serve as an exploitable therapeutic target for patients with BC.
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http://dx.doi.org/10.1186/s12943-021-01359-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045402PMC
April 2021

Application of a "Continuous-Acquisition-Method" to potassium isotope measurement by multi-collector inductively coupled plasma mass spectrometry.

Rapid Commun Mass Spectrom 2021 Apr 14:e9105. Epub 2021 Apr 14.

Ore Deposit and Exploration Center (ODEC), School of Resources and Environmental Engineering, Hefei University of Technology, Hefei, 230009, Anhui, P.R. China.

Rationale: The very small mass difference between K and ArH makes the flat, hydride interference-free peak shoulders very narrow (0.002-0.003 m/z unit), bringing a number of analytical challenges when measuring K isotopic compositions by multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS). In traditional Sequence Run mode, the parameters are loaded every line of the sequence, thus might introduce tiny drifts of tune parameters and mass peaks. This may occasionally lead to the failure of K isotope measurement when mass drifts exceed 0.002 m/z unit. It is thus essential to keep the tune parameters, especially the magnet current, very stable to achieve high precision K isotopic compositions.

Method: We developed a "Continuous-Acquisition-Method" (CAM) MC-ICP-MS Run mode to improve the stability when determining K isotopes. Two sets of experiments were designed: a) Stability test: measuring a single pure K solution (viz. NIST-999c) for ~ 3 hours and comparing the stability of the two run modes; and b) GSB-K test: measuring our inhouse pure K standard solution (GSB-K) in both run modes and comparing the accuracy and precision.

Results: The traditional Sequence Run mode only kept the MC-ICP-MS system stable for the first ~1.5 hours during the ~3 hours test, with an offset of the mass peaks of ~0.003 m/z unit. The CAM Run mode yield higher stability during the whole test (~3 hours), with a peak shift <0.0004 m/z unit. Measurement of GSB-K standard solution in Sequence Run and CAM Run modes gives identical δ K values the when magnet was kept stable, with the CAM Run mode offering a better precision and keeping the instrument stable for longer.

Conclusions: The MC-ICP-MS CAM run mode shows higher stability and better precision. It is, therefore, good for high precision K isotope measurements.
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http://dx.doi.org/10.1002/rcm.9105DOI Listing
April 2021

Establishment and validation of a nomogram model for predicting the survival probability of differentiated thyroid carcinoma patients: a comparison with the eighth edition AJCC cancer staging system.

Endocrine 2021 Apr 6. Epub 2021 Apr 6.

Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, China.

Purpose: This study aimed to develop a clinically predictive nomogram model to predict the survival probability of differentiated thyroid carcinoma patients and compare the value of this model with that of the eighth edition AJCC cancer staging system.

Methods: We selected 59,876 differentiated thyroid carcinoma patients diagnosed between 2004 and 2015 from the SEER database and separated those patients into a training set (70%) and a validation set (30%) randomly. We used Cox regression analysis to build the nomogram model (model 1) and the eighth edition AJCC cancer staging model (model 2). Then we compared the predictive accuracy, discrimination, and clinical usage of both models by calculating AUC (Area under the curve), C-index, as well as analyzing DCA (Decision Curve Analysis) performance respectively.

Results: AUCs of all predicted time points (12-month, 36-month, 60-month, and 120-month) of model 1 were 0.933, 0.913, 0.879, and 0.868 for the training set; 0.933, 0.926, 0.916, and 0.894 for the validation set. As for model 2, data were 0.938, 0.906, 0.866, and 0.847 for the training set; 0.924, 0.925, 0.912, and 0.867 for the validation set. C-indices of model 1 were higher than those of model 2 (0.923 vs. 0.918 for the training set, 0.938 vs. 0.930 for the validation set). DCA comparison showed that the net benefit of model 1 was bigger when comparing with that of model 2.

Conclusions: Model 1 provided with both better predictive accuracy and clinical usage compared with those of model 2 and might be able to predict the survival probability of differentiated thyroid carcinoma patients visually and accurately with a higher net benefit.
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http://dx.doi.org/10.1007/s12020-021-02717-xDOI Listing
April 2021

Relating Gut Microbiome and Its Modulating Factors to Immunotherapy in Solid Tumors: A Systematic Review.

Front Oncol 2021 18;11:642110. Epub 2021 Mar 18.

Division of Medical Oncology, Department of Internal Medicine, University of Kansas Cancer Center, University of Kansas Medical Center, Westwood, KS, United States.

Gut microbiome is proved to affect the activity of immunotherapy in certain tumors. However, little is known if there is universal impact on both the treatment response and adverse effects (AEs) of immune checkpoint inhibitors (ICIs) across multiple solid tumors, and whether such impact can be modulated by common gut microbiome modifiers, such as antibiotics and diet. A systematic search in PubMed followed by stringent manual review were performed to identify clinical cohort studies that evaluated the relevance of gut microbiome to ICIs (response and/or AEs, 12 studies), or association of antibiotics with ICIs (17 studies), or impact of diet on gut microbiome (16 studies). Only original studies published in English before April 1st, 2020 were used. Qualified studies identified in the reference were also included. At the phylum level, patients who had enriched abundance in and almost universally had better response from ICIs, whereas those who were enriched in universally presented with unfavorable outcome. Mixed correlations were observed for in relating to treatment response. Regarding the AEs, correlated to higher incidence whereas were clearly associated with less occurrence. Interestingly, across various solid tumors, majority of the studies suggested a negative association of antibiotic use with clinical response from ICIs, especially within 1-2 month prior to the initiation of ICIs. Finally, we observed a significant correlation of plant-based diet in relating to the enrichment of "ICI-favoring" gut microbiome ( = 0.0476). Gut microbiome may serve as a novel modifiable biomarker for both the treatment response and AEs of ICIs across various solid tumors. Further study is needed to understand the underlying mechanism, minimize the negative impact of antibiotics on ICIs, and gain insight regarding the role of diet so that this important lifestyle factor can be harnessed to improve the therapeutic outcomes of cancer immunotherapy partly through its impact on gut microbiome.
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http://dx.doi.org/10.3389/fonc.2021.642110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012896PMC
March 2021

Molecular Subtypes and CD4 Memory T Cell-Based Signature Associated With Clinical Outcomes in Gastric Cancer.

Front Oncol 2020 17;10:626912. Epub 2021 Mar 17.

Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Background: CD4 memory T cells are an important component of the tumor microenvironment (TME) and affect tumor occurrence and progression. Nevertheless, there has been no systematic analysis of the effect of CD4 memory T cells in gastric cancer (GC).

Methods: Three datasets obtained from microarray and the corresponding clinical data of GC patients were retrieved and downloaded from the Gene Expression Omnibus (GEO) database. We uploaded the normalize gene expression data with standard annotation to the CIBERSORT web portal for evaluating the proportion of immune cells in the GC samples. The WGCNA was performed to identify the modules the CD4 memory T cell related module (CD4 MTRM) which was most significantly associated with CD4 memory T cell. Univariate Cox analysis was used to screen prognostic CD4 memory T cell-related genes (CD4 MTRGs) in CD4 MTRM. LASSO analysis and multivariate Cox analysis were then performed to construct a prognostic gene signature whose effect was evaluated by Kaplan-Meier curves and receiver operating characteristic (ROC), Harrell's concordance index (C-index), and decision curve analyses (DCA). A prognostic nomogram was finally established based on the CD4 MTRGs.

Result: We observed that a high abundance of CD4 memory T cells was associated with better survival in GC patients. CD4 MTRM was used to stratify GC patients into three clusters by unsupervised clustering analysis and ten CD4 MTRGs were identified. Overall survival, five immune checkpoint genes and 17 types of immunocytes were observed to be significantly different among the three clusters. A ten-CD4 MTRG signature was constructed to predict GC patient prognosis. The ten-CD4 MTRG signature could divide GC patients into high- and low-risk groups with distinct OS rates. Multivariate Cox analysis suggested that the ten-CD4 MTRG signature was an independent risk factor in GC. A nomogram incorporating this signature and clinical variables was established, and the C-index was 0.73 (95% CI: 0.697-0.763). Calibration curves and DCA presented high credibility for the OS nomogram.

Conclusion: We identified three molecule subtypes, ten CD4 MTRGs, and generated a prognostic nomogram that reliably predicts OS in GC. These findings have implications for precise prognosis prediction and individualized targeted therapy.
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http://dx.doi.org/10.3389/fonc.2020.626912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011500PMC
March 2021

Prenatal diagnosis and postnatal management of congenital mesoblastic nephroma: Experience at a single center in China.

Prenat Diagn 2021 Mar 29. Epub 2021 Mar 29.

Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University, Guangzhou, Guangdong, China.

Objective: To review the prenatal and postnatal clinical characteristics and pathological subtypes, as well as the surgical outcome for congenital mesoblastic nephroma (CMN) cases.

Method: A retrospective review was performed in 11 cases with CMN prenatally diagnosed at a single center between 2015 and 2019. The clinical characteristics, surgical outcome, histopathology, and follow-up were retrospectively obtained and reviewed.

Results: The median gestational age at which the sonographic diagnosis was made was 35 weeks. Polyhydramnios was found in four (36.4%) cases, and all resulted in a preterm birth. Nine infants had hypertension. Ten cases underwent radical nephrectomy, and one underwent radical nephrectomy and partial adrenalectomy. The pathological results showed that six tumors were classical variants, four mixed variants, and one was a cellular variant. Three cases presented as a stage I, eight as stage II, and no stage III or IV cases were diagnosed. All patients are alive so far. At a median follow-up of 14 months, no local recurrence, or remote metastases were found.

Conclusion: The prognosis of prenatal CMN cases is excellent after early surgery.
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http://dx.doi.org/10.1002/pd.5942DOI Listing
March 2021

Enhanced electrokinetic remediation for Cd-contaminated clay soil by addition of nitric acid, acetic acid, and EDTA: Effects on soil micro-ecology.

Sci Total Environ 2021 Jun 3;772:145029. Epub 2021 Feb 3.

College of Environmental Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, China.

Enhanced electrokinetic remediation (EKR) allows the rapid remediation of heavy metal-contaminated clay, but the impacts of this process on soil micro-ecology have rarely been evaluated. In this study, nitric acid, acetic acid, and EDTA were applied for enhancement of EKR and the effects on Cd removal, soil enzyme activity, and soil bacterial communities (SBCs) were determined. Nitric acid and acetic acid allowed 93.2% and 91.8% Cd removal, respectively, and EDTA treatment resulted in 40.4% removal due to the formation of negatively charged EDTA-Cd complexes, resulting in opposing directions of Cd electromigration and electroosmosis flow and slow electromigration rate caused by low voltage drop. Activities of soil beta-glucosidase, acid phosphatase, and urease, were all reduced by enhanced EKR treatment, especially nitric acid treatment, by 46.2%, 58.8% and 57.7%, respectively. The SBCs were analyzed by high-throughput sequencing and revealed significantly increased diversity for acetic acid treatment, no effect for EDTA treatment, and reduced diversity for nitric acid treatment. Compared with nitric acid and EDTA, acetic acid treatment enhanced EKR for higher Cd removal and improved biodiversity.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145029DOI Listing
June 2021

Characteristics of hydrocarbons in hydrothermal products of the Clam hydrothermal field from the Okinawa trough.

Mar Pollut Bull 2021 Mar 21;167:112277. Epub 2021 Mar 21.

College of Ocean and Meteorology, Guangdong Ocean University, Zhanjiang 524088, China; Laboratory for Coastal Ocean Variation and Disaster Prediction, Guangdong Ocean University, Zhanjiang 524088, China.

The hydrothermal products of the Clam hydrothermal field from the Okinawa Trough were analyzed by gas chromatography-mass spectrometry to determine abundances of hydrocarbons. The n-alkanes in the hydrothermal products conformed to a bimodal distribution and exhibited an odd-to-even predominance of high molecular weight and an even-to-odd predominance of low molecular weight n-alkanes with maxima at C and C. The total concentration of n-alkanes in hydrothermal sediment was much higher than that in hydrothermal sulfide and altered rock. The carbon isotopic value of individual n-alkanes in hydrothermal sediment was slightly higher than that in pelagic sediment. The concentrations and individual carbon isotopic compositions of n-alkanes suggest that the n-alkanes in hydrothermal products may be mainly the result of the metabolic activity of submarine microorganisms. Additionally, the present results suggest that the abiogenic contribution to source of hydrocarbons in hydrothermal products of the Clam hydrothermal field from the Okinawa Trough should not be ignored.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112277DOI Listing
March 2021

Prediction model of random forest for the risk of hyperuricemia in a Chinese basic health checkup test.

Biosci Rep 2021 Apr;41(4)

Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, P.R. China.

Objectives: The present study aimed to develop a random forest (RF) based prediction model for hyperuricemia (HUA) and compare its performance with the conventional logistic regression (LR) model.

Methods: This cross-sectional study recruited 91,690 participants (14,032 with HUA, 77,658 without HUA). We constructed a RF-based prediction model in the training sets and evaluated it in the validation sets. Performance of the RF model was compared with the LR model by receiver operating characteristic (ROC) curve analysis.

Results: The sensitivity and specificity of the RF models were 0.702 and 0.650 in males, 0.767 and 0.721 in females. The positive predictive value (PPV) and negative predictive value (NPV) were 0.372 and 0.881 in males, 0.159 and 0.978 in females. AUC of the RF models was 0.739 (0.728-0.750) in males and 0.818 (0.799-0.837) in females. AUC of the LR models were 0.730 (0.718-0.741) for males and 0.815 (0.795-0.835) for females. The predictive power of RF was slightly higher than that of LR, but was not statistically significant in females (Delong tests, P=0.0015 for males, P=0.5415 for females).

Conclusion: Compared with LR, the good performance in HUA status prediction and the tolerance of features associations or interactions showed great potential of RF in further application. A prospective cohort is necessary for HUA developing prediction. People with high risk factors should be encouraged to actively control to reduce the probability of developing HUA.
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http://dx.doi.org/10.1042/BSR20203859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026814PMC
April 2021

NOGEA: A Network-oriented Gene Entropy Approach for Dissecting Disease Comorbidity and Drug Repositioning.

Genomics Proteomics Bioinformatics 2021 Mar 17. Epub 2021 Mar 17.

College of Life Science, Northwest University, Xi'an 710069, China; College of Life Science, Northwest A & F University, Yangling 712100, China; State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Lianyungang 222001, China. Electronic address:

Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes (DAGs), which are important for understanding disease initiation and developing precision therapeutics. However, DAGs often contain large amounts of redundant or false positive information, leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human diseases. In this study, a network-oriented gene entropy approach (NOGEA) is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene networks. In addition, we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression risk. Master genes may also be used to extract the underlying information of different diseases, thus revealing mechanisms of disease comorbidity. More importantly, approved therapeutic targets are topologically localized in a small neighborhood of master genes on the interactome network, which provides a new way for predicting drug-disease associations. Through this method, 11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated by in vitro experiments. Collectively, the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence, thus providing a valuable strategy for drug efficacy screening and repositioning. NOGEA codes are publicly available at https://github.com/guozihuaa/NOGEA.
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http://dx.doi.org/10.1016/j.gpb.2020.06.023DOI Listing
March 2021

PI3K/Akt/GSK-3β signal pathway is involved in P2X7 receptor-induced proliferation and EMT of colorectal cancer cells.

Eur J Pharmacol 2021 May 15;899:174041. Epub 2021 Mar 15.

Gastrointestinal Surgery, The Second Affiliated Hospital, Nanchang University, Nanchang City, Jiangxi province, China; Molecular Center Key Laboratory, The Second Affiliated Hospital, Nanchang University, Nanchang City, Jiangxi province, China. Electronic address:

P2X7 receptor (P2X7R) plays an important role in regulating the growth of tumor cells. However, the role of P2X7R in colorectal cancer (CRC) has remained poorly understood. Therefore, in this study, in vivo and in vitro experiments were performed to investigate the effect of P2X7R on the proliferation of CRC. The results showed that P2X7R was expressed in CRC cell lines (SW620 and HCT116). ATP and BzATP increased the expression of P2X7R in CRC cells, while the application of P2X7R antagonist A438079 and AZD9056 decreased the P2X7R expression induced by BzATP. Moreover, ATP and BzATP induced the activation of P2X7R to promote the proliferation, migration and invasion of CRC cells. Conversely, A438079, AZD9056 or siRNA transfection targeting P2X7R (siP2X7R) knockdown P2X7R expression inhibited the proliferation and migration of CRC cells. TGF-β1 promoted the migration and invasion of CRC cells, while the application of P2X7R antagonist could inhibit TGF-β1 induced migration of CRC cells. Furthermore, activation of P2X7R increased the expression of Vimentin, Snail, Fibronectin and decreased the expression of E-cadherin. While reducing the expression of P2X7R could inhibit these genes expression. In addition, ATP and BzATP increased the expression of p-Akt, p-GSK-3beta and β-catenin via P2X7R. P13/Akt pathway inhibitor LY294002 inhibited the proliferation of CRC cells, and the P13/Akt signaling was required for BzATP induced the proliferation of CRC cells. Our conclusion is that P2X7R mediated the PI3K/Akt/GSK-3beta signaling to promote the proliferation and EMT of CRC, indicating that P2X7R may be used as a potential therapeutic target for CRC.
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http://dx.doi.org/10.1016/j.ejphar.2021.174041DOI Listing
May 2021

G6PD-NF-κB-HGF Signal in Gastric Cancer-Associated Mesenchymal Stem Cells Promotes the Proliferation and Metastasis of Gastric Cancer Cells by Upregulating the Expression of HK2.

Front Oncol 2021 26;11:648706. Epub 2021 Feb 26.

School of Medicine, Jiangsu University, Zhenjiang, China.

Tumor-associated stromal cells have been widely recognized for their tumor-promoting capability involving paracrine signaling. However, the underlying mechanism and the effects of the molecules in the glycolysis pathway in gastric cancer-associated mesenchymal stem cells (GCMSCs) and gastric cancer cells on tumor progression remain unclear. The expression of hepatocyte growth factor (HGF) in GCMSCs and bone marrow mesenchymal stem cells (BMMSCs) was detected by enzyme-linked immunosorbent assay (ELISA). The effect of HGF derived from GCMSCs on the proliferation, metastasis, and HK2 expression of gastric cancer cells was evaluated and . The effects of G6PD on the production of HGF in mesenchymal stem cells (MSCs) were analyzed by immunoblotting. HGF derived from GCMSCs promoted glycolysis, proliferation, and metastasis of gastric cancer by upregulating c-Myc-HK2 signal. The progression of the disease induced by GCMSCs decelerated in the absence of HK2. The expression of G6PD activated NF-κB signaling and stimulated the production of HGF in GCMSCs. Blocking HGF derived from GCMSCs decreased proliferation, metastasis, and angiogenesis of gastric cancer cells . GCMSCs highly expressed G6PD and facilitated the progression of gastric cancer through the G6PD-NF-κB-HGF axis coordinates. Blocking HGF derived from GCMSCs is a potential new therapeutic target for the treatment of gastric cancer.
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http://dx.doi.org/10.3389/fonc.2021.648706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952978PMC
February 2021

Preliminary study on the evaluation of mitral annulus displacement in normal fetuses by automated cardiac motion quantitation.

J Matern Fetal Neonatal Med 2021 Mar 11:1-9. Epub 2021 Mar 11.

Department of Diagnostic Ultrasound and Echocardiography, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, China.

Objectives: The aim of this study was to assess the characteristics of mitral annular plane systolic excursion (MAPSE) in different longitudinal directions in normal fetuses using a new method, automatic cardiac motion quantification (aCMQ).

Methods: A cross-sectional study was conducted in 164 fetuses with structurally normal hearts. The time-displacement curves of the septal mitral annulus (SMA) in three directions, including point A, B and C (MAPSE-SMA-A, MAPSE-SMA-B, MAPSE-SMA-C), were recorded by aCMQ. The time to peak (TTP) in three directions, including point A, B and C (TTP-SMA-A, TTP-SMA-B, TTP-SMA-C) were recorded. In the same way, various parameters of the lateral mitral annulus (LMA) were obtained including MAPSE-LMA-A, MAPSE-LMA-B, MAPSE-LMA-C, TTP-LMA-A, TTP-LMA-B and TTP-LMA-C. Free angle M-mode echocardiography (FAM) was used to obtain MAPSE of LMA (FAM-MAPSE). Finally, all the data were analyzed statistically.

Results: MAPSE was positively correlated with gestational age, and the difference between the second- and third-trimester groups was statistically significant. MAPSE-LMA in point B and C were greater than those of SMA. MAPSE-LMA-C and MAPSE-SMA-A were the largest in three directions.The difference between point B and C were statistically significant ( .05), with no significant difference at point A ( > .05). There was no significant difference found in all TTP (all  > .05). The MAPSE-LMA-C was less than the FAM-MAPSE, and the differences were found significantly ( < .05), but there was better correlation ( < .05).

Conclusions: The longitudinal movement of the fetal mitral annulus is comprehensive, with multiple directions and different displacements. Perpendicular to the mitral annulus is the maximum displacement. It is positively related to the gestational age. From the second trimester, the longitudinal contraction of the left ventricle wall has good synchronization. It possesses clinical value in selecting different methods and parameters during evaluating left ventricular function.
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http://dx.doi.org/10.1080/14767058.2021.1900102DOI Listing
March 2021

An altered gut microbiota in duck-origin parvovirus infection on cherry valley ducklings is associated with mucosal barrier dysfunction.

Poult Sci 2021 Apr 28;100(4):101021. Epub 2021 Jan 28.

Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China; Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China. Electronic address:

Duck-origin parvovirus disease is an epidemic disease mainly caused by duck-origin goose parvovirus (D-GPV), which is characterized by beak atrophy and dwarfism syndrome. Its main symptoms are persistent diarrhea, skeletal dysplasia, and growth retardation. However, the pathogenesis of Cherry Valley ducks infected by D-GPV has not been studied thoroughly. To perceive the distribution of D-GPV in the intestinal tract, intestinal morphological development, intestinal permeability, inflammatory cytokines in Cherry Valley ducks, and expression of tight junction protein, the D-GPV infection was given intramuscularly. Illumina MiSeq sequencing technology was used to analyze the diversity and structure of ileum flora and content of short-chain fatty acids of its metabolites. To investigate the relationship between intestinal flora changes and intestinal barrier function after D-GPV infection on Cherry Valley ducks is of great theoretical and practical significance for further understanding the pathogenesis of D-GPV and the structure of intestinal flora in ducks. The results showed that D-GPV infection was accompanied by intestinal inflammation and barrier dysfunction. At this time, the decrease of a large number of beneficial bacteria and the content of short-chain fatty acids in intestinal flora led to the weakening of colonization resistance of the intestinal flora and the accumulation of potentially pathogenic bacteria, which would aggravate the negative effect of D-GPV damage to the intestinal tract. Furthermore, a significant increase in Unclassified_S24-7 and decrease in Streptococcus was observed in D-GPV persistent, indicating the disruption in the structure of gut microbiota. Notably, the shift of microbiota was associated with the transcription of tight-junction protein and immune-associated cytokines. These results indicate that altered ileum microbiota, intestinal barrier, and immune dysfunction are associated with D-GPV infection. Therefore, there is a relationship between the intestinal barrier dysfunction and dysbiosis caused by D-GPV, but the specific mechanism needs to be further explored.
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http://dx.doi.org/10.1016/j.psj.2021.101021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940990PMC
April 2021

Fabrication of multicolor Janus microbeads based on photonic crystals and upconversion nanoparticles.

J Colloid Interface Sci 2021 Jun 21;592:249-258. Epub 2021 Feb 21.

Key Laboratory of Carbon Fibers and Functional Polymers, Ministry of Education, Beijing 100029, PR China; Beijing Engineering Research Center for the Synthesis and Applications of Waterborne Polymers, Beijing 100029, PR China; College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China. Electronic address:

In this study, a facile method to fabricate Janus microbeads based on photonic crystals and upconversion nanoparticles is designed. The Janus microbeads can be reversed under magnetic response and generate upconversion fluorescence under near-infrared light. Three kinds of core-shell upconversion nanoparticles (UCNPs) are prepared by the solvothermal method and are mixed with FeO nanoparticles and different sizes of colloidal spheres. The Janus microbeads are assembled according to the hydrophilic property of the mixture and the hydrophobic property of substrates. The upper parts of the Janus microbeads are photonic crystals assembled with colloidal spheres, and the other parts are FeO. Meanwhile, UCNPs are distributed inside the Janus microbeads. Furthermore, the Janus microbeads are prepared into different lattice patterns using special templates. In the lattice patterns, the structural colors of Janus microbeads can be displayed and disappeared by magnetic field inversion, and under external NIR irradiation, Janus microbeads can generate upconversion fluorescence to achieve multiple color display. The Janus microbeads are also applied to both sides of the bank card, and various reading information methods are designed according to different response modes, which have important applications in pattern display, response materials, and anti-counterfeiting.
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http://dx.doi.org/10.1016/j.jcis.2021.02.068DOI Listing
June 2021

Toward human intervention-free clinical diagnosis of intracranial aneurysm via deep neural network.

Patterns (N Y) 2021 Feb 22;2(2):100197. Epub 2021 Jan 22.

BNRist and Department of Automation, Tsinghua University, Beijing, Beijing 100084, China.

Intracranial aneurysm (IA) is an enormous threat to human health, which often results in nontraumatic subarachnoid hemorrhage or dismal prognosis. Diagnosing IAs on commonly used computed tomographic angiography (CTA) examinations remains laborious and time consuming, leading to error-prone results in clinical practice, especially for small targets. In this study, we propose a fully automatic deep-learning model for IA segmentation that can be applied to CTA images. Our model, called Global Localization-based IA Network (GLIA-Net), can incorporate the global localization prior and generates the fine-grain three-dimensional segmentation. GLIA-Net is trained and evaluated on a big internal dataset (1,338 scans from six institutions) and two external datasets. Evaluations show that our model exhibits good tolerance to different settings and achieves superior performance to other models. A clinical experiment further demonstrates the clinical utility of our technique, which helps radiologists in the diagnosis of IAs.
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http://dx.doi.org/10.1016/j.patter.2020.100197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892358PMC
February 2021

200 µJ, 13  ns Er:ZBLAN mid-infrared fiber laser actively Q-switched by an electro-optic modulator.

Opt Lett 2021 Mar;46(5):1141-1144

We report, as far as we know for the first time, on a pulsed 2.7 µm Er:ZBLAN fiber laser -switched by an electro-optic modulator. The -switched operation was achieved with a repetition rate range of 100 Hz-50 kHz. Pulse energy of 205.7 µJ and pulse width down to 13.1 ns, yielding a peak power of 15.7 kW, were obtained at a repetition rate of 100 Hz. The linewidth of the output spectrum was as narrow as 0.4 nm. The pulse width and the pulse peak power, to the best of our knowledge, are currently the shortest and the highest in the 3-µm-band -switched fiber lasers, respectively.
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http://dx.doi.org/10.1364/OL.418950DOI Listing
March 2021

The Copy Number Variation of Regulates Rice Plant Architecture.

Front Plant Sci 2020 11;11:620282. Epub 2021 Feb 11.

Hunan Provincial Key Laboratory of Phytohormones and Growth Development, College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, China.

Copy number variation (CNV) may have phenotypic effects by altering the expression level of the gene(s) or regulatory element(s) contained. It is believed that CNVs play pivotal roles in controlling plant architecture and other traits in plant. However, the effects of CNV contributing to special traits remain largely unknown. Here we report a CNV involved in rice architecture by modulating tiller number and leaf angle. In the genome of ssp. cv. Nipponbare, we found a locus is derived from a 13,002-bp tandem duplication in the nearby region of , a gene regulating tillering in rice. Further survey of 230 rice cultivars showed that the duplication occurred in only 13 rice cultivars. Phenotypic investigation indicated that this CNV region may contribute to tiller number. Moreover, we revealed that not only influences rice tiller number and leaf angle, but also represses transcription in the CNV region. Intriguingly, this CNV performs function through both the dosage and position effects on and . Thus, our work identified a CNV and revealed a molecular regulatory basis for its effects on plant architecture, implying this CNV may possess importance and application potential in molecular breeding in rice.
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http://dx.doi.org/10.3389/fpls.2020.620282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905320PMC
February 2021

Production, immobilization and characterization of beta-glucosidase for application in cellulose degradation from a novel Aspergillus versicolor.

Int J Biol Macromol 2021 Apr 23;177:437-446. Epub 2021 Feb 23.

Laboratory of Medicinal Plant Biotechnology, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China. Electronic address:

Beta-glucosidase (EC 3.2.1.21) catalyzes the hydrolysis of cellobiose and cellooligosaccharides containing (1 → 4)-beta-glycosidic bonds to glucose, which is crucial in cellulosic ethanol production. In this study, Aspergillus versicolor, a novel highly productive beta-glucosidase strain, was first isolated from Camptotheca acuminata seeds. The highest beta-glucosidase activity with 812.86 U/mL was obtained by using the response surface methodology, and a 14.4-fold has increased compared to the control. The beta-glucosidase was then purified to homogeneity with recovery yield and specific activity of 25.98% and 499.15 U/mg, respectively. To enhance its stability and recyclability, the purified beta-glucosidase was first immobilized onto magnetic MnO by electrostatic adsorption. The immobilized materials were characterized by FR-IT, TEM and FE-SEM. Compared with the free beta-glucosidase, the immobilized enzyme exhibited enhanced thermal stability (1.5-fold raise in half-life at 50 °C), and reusability (holding over 60% activity after eight cycles), besides, the optimum pH has increased to 6.0. Substrate specificity research suggested that the enzyme had high hydrolytic activity on cellobiose. It also had a hydrolysis effect on (1 → 3) and (1 → 6)-beta-glycosidic linkages. Application trials in cellulose hydrolysis revealed that the immobilized enzyme was comparatively more effective. Our results suggested this novel immobilized beta-glucosidase makes a promising alternative for the cellulosic ethanol production.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.02.154DOI Listing
April 2021

Accelerating the activation of LiMnO in Li-rich high-Mn cathodes to improve its electrochemical performance.

Nanoscale 2021 Mar;13(9):4921-4930

State key lab of advanced welding and joining, School of Materials Science and Engineering, Harbin Institute of Technology (Shenzhen), Shenzhen 518055, China.

Li-rich high-Mn oxides, xLi2MnO3·(1 - x)LiMO2 (x ≥ 0.5, M = Co, Ni, Mn…), have attracted extensive research interest due to their high specific capacity and low cost. However, slow Li2MnO3 activation and poor cycling stability have affected their electrochemical performance. Herein, to solve these problems, morphology regulation and LiAlF4 coating strategies have been synergistically applied to a Li-rich high-Mn material Li1.7Mn0.8Co0.1Ni0.1O2.7 (HM-811). This dual-strategy successfully promotes the activation process of the Li2MnO3 phase and thus improves the electrochemical performance of HM-811. Theoretical computation indicates that the LiAlF4 layer has a lower Li+ migration barrier than the HM-811 matrix, so it could boost the diffusion of Li+ ions and promote the activation of the Li2MnO3 phase. Benefiting from the morphology regulation and LiAlF4 coating, the HM-811 cathode shows a high initial charge capacity of >300 mA h g-1. In addition, the modified HM-811 could deliver superior electrochemical performance even at a low temperature of -20 °C. This work provides a new approach for developing high performance cathode materials for next-generation Li-ion batteries.
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http://dx.doi.org/10.1039/d0nr08980jDOI Listing
March 2021

Outcomes in older patients with NSCLC receiving immunotherapy: A single center experience.

J Geriatr Oncol 2021 Feb 19. Epub 2021 Feb 19.

Division of Hematology/Oncology, University of Kansas Medical Center, 2650 Shawnee Mission Parkway, Westwood, KS, United States of America.

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http://dx.doi.org/10.1016/j.jgo.2021.02.013DOI Listing
February 2021

Pathological Analysis and Endoscopic Characteristics of Colorectal Laterally Spreading Tumors.

Cancer Manag Res 2021 9;13:1137-1144. Epub 2021 Feb 9.

Department of the Digestive Endoscopy, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550000, People's Republic of China.

Objective: This study aims to analyze the endoscopic and pathological characteristics of colorectal laterally spreading tumors (LSTs) to assist malignant risk stratification to inform selection of the appropriate treatment strategy.

Methods: Patients with colorectal LST were selected as retrospective study objects. Characteristics, including endoscopic findings and the most common site of LSTs of different diameters and histological types, were analyzed. The risk factors for malignancy in colorectal LST were explored by multivariate logistic regression analysis.

Results: LSTs with diameters of ≥20 mm were found mainly in the rectum and mainly with granular-mixed (G-M) morphology (36% and 44.6%, respectively; < 0.05), while LSTs with diameters of <20 mm were found mainly in the ascending colon and mainly with granular-homogenous (G-H) morphology (40.9% and 46.2%, respectively; p < 0.05). Adenoma was the main histological type in patients with tumors of all diameters. However, the cancerization rate of LSTs was 31% in patients with tumor diameter ≥20 mm, while there was no invasive cancer in patients with tumor diameter < 20 mm. In the low-grade dysphasia (adenoma) group, most of the lesions were located in the ascending colon and most had the morphology LST-G-H (35.8% and 39.2%, respectively; p < 0.05). In the cancerization group, most of the lesions were located in the rectum, with the morphology LST-G-M (51.6% and 67.2%, respectively; p < 0.05), and the diameter was larger than that of the adenoma group (33.84 ± 17.99 mm vs 21.68 ± 8.99 mm).

Conclusion: The rectum was the most common site for an LST with a diameter ≥20 mm and cancerization, of which the morphology was mainly LST-G-M (endoscopic submucosal dissection is the preferred treatment for this type of LST). LST malignancy was found to be correlated with lesion diameter, location, and morphological appearance.
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http://dx.doi.org/10.2147/CMAR.S286039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881785PMC
February 2021

Nagashima-Type Palmoplantar Keratosis: Clinical Characteristics, Genetic Characterization, and Clinical Management.

Biomed Res Int 2021 27;2021:8841994. Epub 2021 Jan 27.

Department of Orthopaedics, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, 610041 Sichuan, China.

Nagashima-type palmoplantar keratosis (NPPK) is the most prevalent palmoplantar keratoderma (PPK) in East Asia. Homozygous or compound heterozygous loss-of-function mutations in serpin peptidase inhibitor, clade B (ovalbumin), and member 70 (SERPINB7), which encodes members of the serine protease inhibitor superfamily, have been identified as the cause of NPPK. Clinical manifestations of NPPK include well-demarcated erythema, mild to moderate hyperkeratosis on the whole palm, and sole with transgrediens, extending to the dorsal surfaces of the hands and feet, inner wrists, ankles, and the Achilles tendon areas. In this study, we perform a review of relevant clinical cases aimed at elucidating the clinical characteristics, genetic characterization, differential diagnoses, and clinical management of NPPK. A better understanding of the clinical characteristics and pathogenic gene characterization of NPPK will enhance the diagnosis of NPPK, identify related diseases, and inform on the precise therapy and prognosis. Moreover, it will promote the awareness of NPPK in non-Asian regions.
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http://dx.doi.org/10.1155/2021/8841994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861918PMC
January 2021

Characterization of an antioxidant pectic polysaccharide from Platycodon grandiflorus.

Int J Biol Macromol 2021 Apr 8;175:473-480. Epub 2021 Feb 8.

Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China; Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, PR China. Electronic address:

Platycodonis Radix is widely used as homology of medicine and food in China; polysaccharides are thought to be one of its functional constituents. In this study, a pectic polysaccharide, PGP-I-I, was obtained from the root of the traditional medicine plant Platycodon grandiflorus through ion exchange chromatography and gel filtration. This was characterized being mainly composed of 1,5-α-L-arabinan and both arabinogalactan type I (AG-I) and II chains linked to rhamnogalacturonan I (RG-I) backbone linked to longer galacturonan chains. In vitro bioactivity study showed that PGP-I-I could restore the intestinal cellular antioxidant defense under the condition of hydrogen peroxide (HO) treatment through promoting the expressions of cellular antioxidant genes and protect against oxidative damages.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.02.041DOI Listing
April 2021

[Genetic testing and prenatal diagnosis for a pedigree affected with tuberous sclerosis complex].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Feb;38(2):154-157

Central Laboratory, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu 215002, China. com.

Objective: To explore the genetic basis for Chinese pedigree affected with tuberous sclerosis complex (TSC).

Methods: The proband and his family members were subjected to Sanger sequencing for variants of the TSC1 and TSC2 genes.

Results: The proband was found to harbor a c.2837+1dupG splicing variant at a donor site of the TSC2 gene. The same variant was not found among his family members and the fetus during his mother's subsequent pregnancy.

Conclusion: The c.2837+1dupG splicing variant of the TSC2 gene has probably predisposed to the TSC in this pedigree. Above finding has enriched the spectrum of pathogenic variants associated with this disease.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200331-00227DOI Listing
February 2021

Protective Effect of Vitamin E on Cadmium-Induced Renal Oxidative Damage and Apoptosis in Rats.

Biol Trace Elem Res 2021 Feb 9. Epub 2021 Feb 9.

College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, People's Republic of China.

Cadmium (Cd), a widely distributed heavy metal, is extremely toxic to the kidney. Vitamin E (VE) is an important antioxidant in the body. It is known that VE exerts a protective effect on renal oxidative damage caused by Cd, but the effect and mechanism of VE on apoptosis are not fully understood. Thus, we conducted this study to explore the protective effect of VE on Cd-induced renal apoptosis and to elucidate its potential mechanism. Thirty-two 9-week-old male Sprague-Dawley rats were randomly divided into four groups, namely control, VE (100 mg/kg VE), Cd (5 mg/kg CdCl), and VE + Cd (100 mg/kg VE + 5 mg/kg CdCl), and received intragastric administration of Cd and/or VE for 4 weeks. The results showed that Cd exposure significantly reduced the weight of the body and kidney, elevated the accumulation of Cd in the kidney as well as the levels of BUN and Scr in serum, caused renal histological alterations, decreased the GSH and T-AOC contents and antioxidant enzyme (SOD, CAT, GSH-PX) activities, and increased renal MDA content. And the increased number of TUNEL-positive cells by Cd was accompanied by upregulated mRNA and protein expressions of apoptotic regulatory molecules (Bax, Caspase-3, GRP94, GRP78, Caspase-8) and downregulated Bcl-2 expressions. However, the combined treatment of Cd and VE could restore the above parameters to be close to those in the control rats. In conclusion, VE supplement could alleviate Cd-induced rat renal damage and oxidative stress through enhancing the antioxidant defense system and inhibiting apoptosis of renal cells.
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http://dx.doi.org/10.1007/s12011-021-02606-4DOI Listing
February 2021