Publications by authors named "Jin Yang"

1,850 Publications

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Identification of four gastric cancer subtypes based on genetic analysis of cholesterogenic and glycolytic pathways.

Bioengineered 2021 Dec;12(1):4780-4793

Department of Gastrointestinal Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.

Warburg phenomenon refers to the development of unique metabolic patterns during the growth of tumor cells. This study stratified gastric cancer into prognostic metabolic subgroups according to changes in gene expressions related to glycolysis and cholesterol synthesis. The RNA-seq expression data, single nucleotide variants (SNV), short insertions and deletions (InDel) mutation data, copy number variation (CNV) data and clinical follow-up information data of gastric cancer tissues were downloaded from The Cancer Genome Atlas (TCGA) database. ConsensusClusterPlus was used to stratify the metabolic subtypes of gastric cancer. Four metabolic subtypes (Cholesterogenic, Glycolytic, Mixed and Quiescent) of gastric cancer were identified, and patients with cholesterogenic tumors had the longest disease-specific survival (DSS). Genome-wide analysis showed that aberrant amplification of TP53 and MYC in gastric cancer was associated with abnormal cholesterol anabolic metabolism. The mRNA levels of mitochondrial pyruvate carriers 1 and 2 (MPC1/2) differed among the four subtypes. Tumors in the glycolytic group showed a higher PDCD1. A genomic signature based on tumor metabolism of different cancer types was established. This study showed that genes related to glucose and lipid metabolism play an important role in gastric cancer and facilitate a personalized treatment of gastric cancer.
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http://dx.doi.org/10.1080/21655979.2021.1956247DOI Listing
December 2021

Extracellular Vesicle Transportation and Uptake by Recipient Cells: A Critical Process to Regulate Human Diseases.

Processes (Basel) 2021 Feb 31;9(2). Epub 2021 Jan 31.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University Medical Campus, Boston, MA 02118, USA.

Emerging evidence highlights the relevance of extracellular vesicles (EVs) in modulating human diseases including but not limited to cancer, inflammation, and neurological disorders. EVs can be found in almost all types of human body fluids, suggesting that their trafficking may allow for their targeting to remote recipient cells. While molecular processes underlying EV biogenesis and secretion are increasingly elucidated, mechanisms governing EV transportation, target finding and binding, as well as uptake into recipient cells remain to be characterized. Understanding the specificity of EV transport and uptake is critical to facilitating the development of EVs as valuable diagnostics and therapeutics. In this mini review, we focus on EV uptake mechanisms and specificities, as well as their implications in human diseases.
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http://dx.doi.org/10.3390/pr9020273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323758PMC
February 2021

BZW2/5MP1 acts as a promising target in hepatocellular carcinoma.

J Cancer 2021 22;12(17):5125-5135. Epub 2021 Jun 22.

Department of Translational Medicine Center, Affiliated Hospital of Hangzhou Normal University, Institute of Hepatology and Metabolic Diseases of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.

Basic leucine zipper and W2 domain 2 (BZW2), also known as 5MP1, is a protein related to translation regulation. Evidence from previous studies indicates that BZW2 is involved in tumorigenesis in several cancers. However, little is known about the role of BZW2 in hepatocellular carcinoma (HCC). In this study, we first analyzed the gene expression profile of BZW2 in multiple HCC datasets. Next, we explored the biological effects of BZW2 in HCC cell lines. BZW2 was overexpressed in different HCC cohorts. Multivariate analysis confirmed that increased BZW2 expression is an independent prognostic indicator of shorter overall survival. BZW2 coexpressed genes were mainly enriched in the biological processes of ribonucleoprotein complex biogenesis, rRNA metabolism, translational initiation, and negative regulation of metabolic processes. BZW2 depletion reduced proliferation, clonality, and invasion and increased apoptosis in MHCC97-H cells. Furthermore, BZW2 overexpression or knockdown enhanced or impaired c-Myc expression, respectively. Overall, these findings identified BZW2 as a biomarker of HCC and provided novel insight that the effect of BZW2 on the translatome is a potential mechanism that promotes HCC progression via the c-Myc pathway.
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http://dx.doi.org/10.7150/jca.53282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317536PMC
June 2021

Deciphering the Taxonomic Delimitation of (Hydrocharitaceae) Using Complete Plastomes as Super-Barcodes.

Front Plant Sci 2021 15;12:681270. Epub 2021 Jul 15.

School of Life Sciences, Yunnan Normal University, Kunming, China.

Accurate species delimitation and identification, which is a challenging task in traditional morphology-based taxonomy, is crucial to species conservation. (Hydrocharitaceae) is a severely threatened submerged macrophyte endemic to southwestern China. The taxonomy of , which has long been in dispute, remains unresolved, impeding effective conservation and management practices. Here, we aim to address the long-standing issues concerning species boundary and intraspecific subdivision of using complete plastome sequences as super-barcodes. The taxonomic delimitation of was explored using phylogenetic inference and two independent sequence-based species delimitation schemes: automatic barcode gap discovery (ABGD) and multi-rate Poisson tree processes (mPTP). The reciprocally reinforcing results support the reduction of the closely related congeneric species, and , as two conspecific varieties of . Within the newly defined , accurate varietal identification can be achieved using plastome super-barcodes. These findings will help inform future decisions regarding conservation, management and restoration of . This case study suggests that the use of plastome super-barcodes can provide a solution for species delimitation and identification in taxonomically difficult plant taxa, thus providing great potential to lessen the challenges of inventorying biodiversity, as well as biologically monitoring and assessing threatened species.
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http://dx.doi.org/10.3389/fpls.2021.681270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320023PMC
July 2021

Ionizing radiation-induced 'zombie' carcinoma-associated fibroblasts with suppressed pro-radioresistance on OSCC cells.

Oral Dis 2021 Jul 29. Epub 2021 Jul 29.

State Key Laboratory of Oral Diseases & National Center of Stomatology & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Objectives: This study was to investigate the effect of ionizing radiation (IR) on oral carcinoma-associated fibroblasts (CAFs) and to further explore subsequent effects of IR-induced 'zombie' CAFs on oral squamous cell carcinoma (OSCC) cells.

Materials And Methods: Three primary CAFs and one primary normal-associated fibroblasts (NAFs) were separated from human OSCC and normal oral mucosa tissues, identified by immunocytochemistry. Cells were exposed to IR by X-ray irradiator under different doses. The DNA damage, proliferation and migration of irradiated CAFs were respectively detected by immunofluorescence and wound healing assay, while senescence detected by β-galactosidase staining. Finally, the effect of irradiated CAFs on biological behavior and radioresistance of Cal-27 cells were determined via assays mentioned above.

Results: Oral CAFs were sensitive to IR with DNA damage increasing and proliferation decreasing. 18 Gy IR could not kill oral CAFs but induce them to 'zombies', with arrested proliferation, increased senescence and reduced migration. 'Zombie' CAFs (zCAFs) could enhance proliferation, migration and invasion of Cal-27 cells, and show suppressed pro-radioresistance by reducing DNA damage and facilitating survival.

Conclusions: IR-induced zCAFs could continuously promote radioresistance of OSCC cells though being suppressed, suggesting the potential promoting effect on tumor relapse post-radiotherapy that needed further exploring.
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http://dx.doi.org/10.1111/odi.13979DOI Listing
July 2021

COVID-19 vaccination in Chinese children: a cross-sectional study on the cognition, psychological anxiety state and the willingness toward vaccination.

Hum Vaccin Immunother 2021 Jul 29:1-7. Epub 2021 Jul 29.

Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

It is important to understand the cognition, willingness, and psychological anxiety state of Chinese guardians toward COVID-19 vaccination for their children to predict the future vaccination rate and to help the design of policies that aim to expand the population with immunity against COVID-19. This study collected data with a professional vaccination registration platform for children named "Xiao Dou Miao" in February 2021. The psychological anxiety state of the guardians was self-evaluated using the psychological anxiety scale. Factors that might influence the willingness of guardians to vaccinate their children were identified using logistic regression analysis. This study included 12,872 questionnaires with 70.9% of guardians showing willingness to vaccinate their children. Guardians who were male, aged 40-49 and from rural area were more willing to vaccinate their children. Fathers, guardians with higher education and income, whose children have a history of adverse vaccine reactions and allergies were less willing to vaccinate their children ( < .001). More than 80% of the guardians expressed a high level of trust for vaccine information released by official and health-related agencies. Guardians who were not vaccinated were more anxious than those who were vaccinated (χ2 = 27.99, < .001). To protect children from COVID-19, vaccine coverage in children should be expanded rapidly and public awareness on vaccine safety and effectiveness should be improved.
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http://dx.doi.org/10.1080/21645515.2021.1949950DOI Listing
July 2021

A Porous Metal-Organic Framework as an Electrochemical Sensing Platform for Highly Selective Adsorption and Detection of Bisphenols.

Inorg Chem 2021 Jul 27. Epub 2021 Jul 27.

Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education, Faculty of Chemistry, Northeast Normal University, Changchun, Jilin 130024, China.

The design of artificial receptors with a specific recognition function and enhanced selectivity is highly desirable in the electrochemical sensing field, which can be used for detection of environmental pollutants. In this facet, metal-organic frameworks (MOFs) featured adjustable porosities and specific host-guest recognition properties. Especially, the large hydrophobic cavity formed in the porous MOFs may become a potential artificial receptor. We herein designed a new porous MOF [Zn(L)(IPA)(HO)]·2DMF·2MeOH·3HO () by using a functionalized sulfonylcalix[4]arene () and isophthalic acid (HIPA) (DMF = ,'-dimethylformamide). The specific pore size and pore shape of made it efficiently selective for absorption of bisphenol A (), bisphenol F (), and bisphenol S (). Therefore, a rapid, highly selective, and ultrasensitive electrochemical sensing platform was fabricated by using as a host to recognize and absorb bisphenol guests ( = graphite powder, = glassy carbon electrode). Most strikingly, the extremely low detection limits were up to 3.46 and 0.17 nM for and , respectively, using the electrode. Furthermore, the "recognition and adsorption" mechanism was uncovered by density functional theory with the B3LYP function. This work offered a prospective strategy for selective absorption and detection of harmful bisphenols with the MOF-based porous material.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01253DOI Listing
July 2021

Development and Validation of a Ferroptosis-Related Gene Signature for Overall Survival Prediction in Lung Adenocarcinoma.

Front Cell Dev Biol 2021 7;9:684259. Epub 2021 Jul 7.

Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Ferroptosis is an iron-dependent programmed cell death process. Recent studies have found that ferroptosis inducers hold promising potential in the treatment of lung adenocarcinoma (LUAD). However, the comprehensive analysis about the prognostic value of ferroptosis-related genes in LUAD remains to be elucidated. The RNA sequencing data and corresponding clinical information were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A total of 259 ferroptosis-related genes were extracted from FerrDb website. The ferroptosis-related prognostic signature was developed by least absolute shrinkage and selection operator (LASSO) Cox regression analysis in TCGA LUAD cohort, and then validated by 5 independent GEO cohorts. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were performed to identify the difference in biological processes and functions between different risk groups. The expression levels of core prognostic genes were then verified in LUAD samples by immunohistochemistry (IHC) and erastin-treated LUAD cell lines by real-time polymerase chain reaction (PCR). The potential roles of GPX2 and DDIT4 as ferroptosis drivers in LUAD cell line were further confirmed by experiments. A total of 20 intersecting genes between 70 ferroptosis-related DEGs and 45 potential prognostic genes were obtained for LASSO Cox regression analysis. The ferroptosis-related prognostic signature was developed by 7 core prognostic DEGs, and stratified LUAD patients into two risk groups. Kaplan-Meier analysis showed that the overall survival (OS) of LUAD patients in the high-risk group was significantly worse than that of the low-risk group. External validation of 5 independent GEO cohorts further confirmed that the ferroptosis-related prognostic signature was an ideal biomarker for predicting the survival of LUAD patients. Significant enrichment of fatty acid metabolism and cell cycle-related pathways were found in different risk groups. The expression patterns of 7 core prognostic genes in LUAD and adjacent normal lung tissues were validated by IHC, which was almost consistent with the results from public database. Furthermore, the changes related to cell cycle and ferroptosis after erastin treatment were also validated in LUAD cell lines. In addition, silencing GPX2 or DDIT4 could partially reverse the erastin-induced ferroptosis. In summary, the ferroptosis-related prognostic signature based on 7 core prognostic DEGs indicated superior predictive performance of LUAD patients. Targeting ferroptosis holds potential to be a therapeutic alternative for LUAD.
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http://dx.doi.org/10.3389/fcell.2021.684259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294813PMC
July 2021

FBP1 enhances the radiosensitivity by suppressing glycolysis via the FBXW7/mTOR axis in nasopharyngeal carcinoma cells.

Life Sci 2021 Jul 20;283:119840. Epub 2021 Jul 20.

Department of Oncology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address:

Aims: The high glycolysis state of tumor cells is closely related to radioresistance. Fructose-1,6-bisphosphatase (FBP1) can regulate aerobic glycolysis and exerts tumor suppressor effects in many cancers, but its role in nasopharyngeal carcinoma (NPC) remains to be investigated.

Materials And Methods: RT-qPCR was used to measure FBP1 mRNA level. Glucose consumption, lactic acid production and ATP level was determined to evaluate glycolysis. The sensitivity of NPC cells to radiation was analyzed by MTT assay. Apoptosis was performed using flow cytometry. Gain- and loss-of function assays were carried out to explore the specific role of FBP1 and FBXW7 (F-box and WD repeat domain-containing 7) in NPC cell functions. The interactions between FBXW7 and FBP1 or mTOR were validated with co-immunoprecipitation assay. The in vivo experiments with xenografts were used to evaluate the role of FBP1 in tumor growth.

Key Findings: FBP1 expression was lower in NPC tissues and cells than in normal controls and nasopharyngeal epithelial cells. Human recombinant FBP1 (rh-FBP1) treatment suppressed glycolysis in NPC cells. Besides, silencing FBP1 weakened the radiosensitivity and alleviated radiation-induced apoptosis and DNA damage by promoting glycolysis. Mechanism exploration found that FBP1 promoted FBXW7 protein level through suppressing the autoubiquitination of FBXW7. Then, FBXW7 restrained mTOR level by facilitating mTOR ubiquitination, thereby suppressing glycolysis and promoting radiation-induced apoptosis and DNA damage. Furthermore, overexpressing FBP1 in vivo hindered tumor growth and enhanced the antitumor activity of radiation.

Significance: FBP1 promoted the radiosensitivity in NPC cells by inhibiting glycolysis through the FBXW7/mTOR axis.
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http://dx.doi.org/10.1016/j.lfs.2021.119840DOI Listing
July 2021

Development and validation of an immune gene set-based prognostic signature in cutaneous melanoma.

Future Oncol 2021 Jul 22. Epub 2021 Jul 22.

Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.

We aimed to fully understand the landscape of the skin cutaneous melanoma (SKCM) microenvironment and develop an immune prognostic signature that can predict the prognosis for SKCM patients. RNA sequencing data and clinical information were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus databases. The immune-prognostic signature was constructed by LASSO Cox regression analysis. We calculated the relative abundance of 29 immune-related gene sets based on the mRNA expression profiles of 314 SKCM patients in the Cancer Genome Atlas training set. Hierarchical clustering was performed to classify SKCM patients into three clusters: immunity-high, -medium and -low. The values of our prognostic model in predicting disease progression, metastasis and immunotherapeutic responses were also validated. In conclusion, the prognostic model demonstrated a powerful ability to distinguish and predict SKCM patients' prognosis.
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http://dx.doi.org/10.2217/fon-2021-0104DOI Listing
July 2021

Association between serum TNF-α and sarcopenia in liver cirrhosis.

Clin Mol Hepatol 2021 Jul 20. Epub 2021 Jul 20.

Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background/aims: Sarcopenia is an independent prognostic factor of liver cirrhosis (LC). However, the association between LC-related systemic inflammation and sarcopenia is unclear.

Methods: Sprague-Dawley rats were treated with thioacetamide (TAA) or saline as a control. Rifaximin was administered to TAA-induced rats. ELISA was performed to measure inflammatory mediators in rat serum. RT-PCR was performed to measure the molecular expression in tissues. Hematoxylin and eosin (H&E) staining and immunohistochemistry were performed to investigate tissue pathology. Serum tumor necrosis factor-α (TNF-α) levels, liver stiffness (LS), and the L3 skeletal muscle index (L3SMI) were measured in 60 patients with chronic liver disease (CLD).

Results: LC and sarcopenia were successfully induced by TAA. Serum TNF-α levels were increased in LC rats and correlated with myostatin expression, muscle weight, and myofiber diameter. The expression of intestinal occludin and ZO-1 was reduced in LC rats and was associated with serum TNF-α levels and sarcopenia. In patients with LS≥7 kPa or sarcopenia, serum TNF-α levels were significantly increased, which was also confirmed when we raised the LS cutoff to 10 kPa. The value of the L3SMI was inversely correlated with serum TNF-α levels in patients with LS≥7 kPa. TNF-α was reduced by rifaximin, which might have resulted in reduced expression of muscular MuRF1 and myostatin and improvements in myofiber diameters within muscle tissues.

Conclusions: These results suggest that TNF-α is associated with LC-related sarcopenia. Rifaximin might be effective in reducing TNF-α levels and improving sarcopenia in LC, but these results need to be validated in future studies.
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http://dx.doi.org/10.3350/cmh.2021.0082DOI Listing
July 2021

Clinical value of alkaline phosphatase on the surface membrane of neutrophils for prediction of bacteremia in patients with systemic inflammatory response syndrome.

Diagn Microbiol Infect Dis 2021 Aug 4;100(4):114105. Epub 2016 Jun 4.

Department of Central Laboratory, the First People's Hospital of Lianyungang, Lianyungang, China.

In this study, the utility and diagnostic accuracy of alkaline phosphatase on the surface membrane of neutrophils (mNAP) for bacteremia in patients with systemic inflammatory response syndrome (SIRS) was investigated and assessed. A total of 149 patients with SIRS were included. mNAP values were significantly higher in bacteremic SIRS group compared with that in non-bacteremic SIRS group (P < 0.001). The mNAP levels were significantly higher in SIRS patients with gram-negative bacteremia than those with gram-positive bacteremia. (P < 0.001). The receiver operating characteristic (ROC) curve analysis revealed the areas under ROC (AUC) of 0.806 for mNAP in differentiating SIRS patients with bacteremia from those without, similar to that for procalcitonin (PCT) (0.797). Combination of PCT and mNAP gave an AUC of 0.841. mNAP shares a similar diagnostic accuracy to PCT in predicting bacteremia in SIRS patients. The combination of mNAP and PCT provides a better prediction of bacteremia in patients with SIRS than either test alone.
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http://dx.doi.org/10.1016/j.diagmicrobio.2016.05.022DOI Listing
August 2021

Experimental Study of the Impact of Chlorine Dioxide on the Permeability of High-Rank Contaminated Coal Reservoirs.

ACS Omega 2021 Jul 1;6(27):17314-17322. Epub 2021 Jul 1.

School of Resources and Environment, Henan Polytechnic University, Jiaozuo 454000, China.

The permeability of high-rank coal reservoirs is generally low, and high-viscosity working fluid can also contaminate the reservoirs and reduce permeability during drilling and fracturing engineering. These two reasons lead to a lot of low-yield CBM wells in the southern Qinshui Basin, China. The impact of chlorine dioxide on the permeability of high-rank coal has been studied in detail. The coal samples with changed characteristics before and after treatment were compared using coal-ash, displacement, immersion, and plug removal experiments. The ash experiment results show that the ash content of the coal samples decreased by 16.35%. The displacement and immersion experiments using chlorine dioxide solution showed that displacement with chlorine dioxide could increase permeability. The permeability of coal samples increased by 3005.77% after 80 h of immersion. The plug removal experiment results show that the permeability of contaminated coal samples was recovered by 11.10-38.90%, with an average recovery of 27.90%. The experimental results show that chlorine dioxide is effective in improving the permeability of high-rank contaminated coal reservoirs. This research result can be applied to low-yield CBM wells polluted by high-viscous working fluid to increase gas production.
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http://dx.doi.org/10.1021/acsomega.1c01348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280684PMC
July 2021

Functional analysis of deleterious SNPs in lens epithelial cells.

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

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

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

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

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

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

Permeable characteristics of surface film deposited on LiMnO positive electrode revealed by redox-active indicator.

Nano Converg 2021 Jul 14;8(1):21. Epub 2021 Jul 14.

Department of Energy Engineering, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea.

Herein, the ferrocene redox indicator-based surface film characteristics of spinel lithium manganese oxide (LMO) were evaluated. The pre-cycling of spinel LMO generated a film on the LMO surface. The surface film deposited on LMO surface suppresses further electrolyte decomposition, while the penetration of approximately 0.7 nm-sized redox indicator is not prevented. The facile self-discharge of LMO and regeneration current from the ferrocenium molecule was observed from the redox indicator in a specifically designed four-electrode cell. From this electrochemical behavior, a small-sized HF molecule attack on the LMO surface through a carbonate-based electrolyte-derived film is defined; hence, the prevention of small-sized molecules into the deposited surface film is crucial for the enhancement of LiMnO-based lithium-ion batteries.
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http://dx.doi.org/10.1186/s40580-021-00272-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280264PMC
July 2021

Programmable Unlocking Nano-Matryoshka-CRISPR Precisely Reverses Immunosuppression to Unleash Cascade Amplified Adaptive Immune Response.

Adv Sci (Weinh) 2021 07 14;8(13):2100292. Epub 2021 May 14.

State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610041 P. R. China.

Immune checkpoint blockade (ICB) is an attractive option in cancer therapy, but its efficacy is still less than expected due to the transient and incomplete blocking and the low responsiveness. Herein, an unprecedented programmable unlocking nano-matryoshka-CRISPR system (PUN) targeting programmed cell death ligand 1 (PD-L1) and protein tyrosine phosphatase N2 (PTPN2) is fabricated for permanent and complete and highly responsive immunotherapy. While PUN is inert at normal physiological conditions, enzyme-abundant tumor microenvironment and preternatural intracellular oxidative stress sequentially trigger programmable unlocking of PUN to realize a nano-matryoshka-like release of CRISPR/Cas9. The successful nucleus localization of CRISPR/Cas9 ensures the highly efficient disruption of PD-L1 and PTPN2 to unleash cascade amplified adaptive immune response via revoking the immune checkpoint effect. PD-L1 downregulation in tumor cells not only disrupts PD-1/PD-L1 interaction to attenuate the immunosurveillance evasion but also spurs potent immune T cell responses to enhance adaptive immunity. Synchronously, inhibition of JAK/STAT pathway is relieved by deleting PTPN2, which promotes tumor susceptibility to CD8 T cells depending on IFN-, thus further amplifying adaptive immune responses. Combining these advances together, PUN exhibits optimal antitumor efficiency and long-term immune memory with negligible toxicity, which provides a promising alternative to current ICB therapy.
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http://dx.doi.org/10.1002/advs.202100292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261501PMC
July 2021

Dynamic changes of functional fitness, antibodies to SARS-CoV-2 and immunological indicators within 1 year after discharge in Chinese health care workers with severe COVID-19: a cohort study.

BMC Med 2021 07 14;19(1):163. Epub 2021 Jul 14.

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China.

Background: Few studies had described the health consequences of patients with coronavirus disease 2019 (COVID-19) especially in those with severe infections after discharge from hospital. Moreover, no research had reported the health consequences in health care workers (HCWs) with COVID-19 after discharge. We aimed to investigate the health consequences in HCWs with severe COVID-19 after discharge from hospital in Hubei Province, China.

Methods: We conducted an ambidirectional cohort study in "Rehabilitation Care Project for Medical Staff Infected with COVID-19" in China. The participants were asked to complete three physical examinations (including the tests of functional fitness, antibodies to SARS-CoV-2 and immunological indicators) at 153.4 (143.3, 164.8), 244.3 (232.4, 259.1), and 329.4 (319.4, 339.3) days after discharge, respectively. Mann-Whitney U test, Kruskal-Wallis test, t test, one-way ANOVA, χ, and Fisher's exact test were used to assess the variance between two or more groups where appropriate.

Results: Of 333 HCWs with severe COVID-19, the HCWs' median age was 36.0 (31.0, 43.0) years, 257 (77%) were female, and 191 (57%) were nurses. Our research found that 70.4% (114/162), 48.9% (67/137), and 29.6% (37/125) of the HCWs with severe COVID-19 were considered to have not recovered their functional fitness in the first, second, and third functional fitness tests, respectively. The HCWs showed improvement in muscle strength, flexibility, and agility/dynamic balance after discharge in follow-up visits. The seropositivity of IgM (17.0% vs. 6.6%) and median titres of IgM (3.0 vs. 1.4) and IgG (60.3 vs. 45.3) in the third physical examination was higher than that in the first physical examination. In the third physical examination, there still were 42.1% and 45.9% of the HCWs had elevated levels of IL-6 and TNF-α, and 11.9% and 6.3% of the HCWs had decreased relative numbers of CD3 T cells and CD4 T cells.

Conclusion: The HCWs with severe COVID-19 showed improvement in functional fitness within 1 year after discharge, active intervention should be applied to help their recovery if necessary. It is of vital significance to continue monitoring the functional fitness, antibodies to SARS-CoV-2 and immunological indicators after 1 year of discharge from hospital in HCWs with severe COVID-19.
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http://dx.doi.org/10.1186/s12916-021-02042-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277525PMC
July 2021

The enhancement mechanism of ultra-active AgPO modified by tungsten and the effective degradation towards phenolic pollutants.

Chemosphere 2021 Jul 6;285:131440. Epub 2021 Jul 6.

Department of Chemical Engineering, Sichuan University, Chengdu, Sichuan, 610065, China; Engineering Research Center for Comprehensive Utilization and Cleaning Process of Phosphate Resource, Ministry of Education, Chengdu, 610065, China.

A novel strategy of W modification was applied to overcome the disadvantages of AgPO. Ultra-active AgPO with different W doping ratios were successfully synthesized by facile chemical precipitation method, among which 0.5%W-AP showed the best results. Meanwhile, the stability and yield were enhanced. XRD, Raman and ESR etc. were employed to investigate the morphology, structure and optical properties of samples. It was proved W entered into the AgPO lattice, occupied the position of P and doped in the form of WO. The significant improvement of photocatalytic performance of W doped AgPO was attributed to the change of morphology, the decrease of particle size, the increase of crystallinity, the shrink of band gap energy and the reduction of photo-induced carriers recombination rate with W doping. The photocatalytic mechanism analysis showed h was the main oxidative species in the photocatalytic process, •O and •OH played minor roles. Under visible light irradiation, the impacts of the important operating parameters on the typical phenolic pollutants, phenol and bisphenol A, were evaluated with 0.5%W-AP. It was confirmed that 68% and 82% of phenol and bisphenol A were respectively degraded within 15 min and 40 min under optimized photocatalytic parameters: 0.4 g/L catalyst dosage, 20 mg/L pollutant concentration, pH 5.7 and 125 mW/cm irradiation intensity, and the corresponding K' were 2.14 and 5.50 times of undoped samples. This work provides a new approach for effective degradation towards phenolic pollutants by AgPO with ultra-high photocatalytic activity, high applicability and enhanced stability and yield.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131440DOI Listing
July 2021

A novel 4-gene signature model simultaneously predicting malignant risk of oral potentially malignant disorders and oral squamous cell carcinoma prognosis.

Arch Oral Biol 2021 Jun 30;129:105203. Epub 2021 Jun 30.

State Key Laboratory of Oral Diseases, National Center of Stomatology, National Clinical Research Center for Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China.

Objective: Oral squamous cell carcinoma (OSCC) is often diagnosed at late stage with a poor prognosis. The study hereunder aimed to construct a multi-gene model to simultaneously promote early diagnosis of OSCC by evaluating malignant risk of oral potentially malignant disorders (OPMDs) and predict prognosis.

Materials And Methods: 3 GEO datasets including OPMDs and OSCC samples were obtained for overlapping differentially expressed genes (DEGs) being screened. The predictive model was built with optimal DEGs by SVM algorithm, estimated by receiver operator characteristic curves and validated for double prediction via oral cancer-free survival (for malignant risk of OPMDs) and overall survival time (for OSCC) analysis respectively compared to other models. The protein expression of biomarkers in the model was validated in human samples by immunohistochemistry.

Results: A novel predictive model of 4-gene signature was built based on 12 common DEGs revealed from 3 GEO datasets. It could well distinguish OSCC from OPMDs and normal tissues. Both oral cancer-free survival and overall survival time analysis were significantly poorer in high-risk patients than in low-risk ones in Kaplan Meier survival curve respectively. The protein expression of biomarkers in OSCC was with significant difference compared to normal and OPMDs.

Conclusions: The novel 4-gene signature model presents strong ability in simultaneous prediction of the malignant risk of OPMDs and OSCC progression, potentially benefiting both the early diagnosis and therapeutic outcomes of OSCC.
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http://dx.doi.org/10.1016/j.archoralbio.2021.105203DOI Listing
June 2021

Comparison of Residual Pulmonary Abnormalities 3 Months After Discharge in Patients Who Recovered From COVID-19 of Different Severity.

Front Med (Lausanne) 2021 25;8:682087. Epub 2021 Jun 25.

NHC Key Laboratory of Pulmonary Diseases, Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

To investigate whether coronavirus disease 2019 (COVID-19) survivors who had different disease severities have different levels of pulmonary sequelae at 3 months post-discharge. COVID-19 patients discharged from four hospitals 3 months previously, recovered asymptomatic patients from an isolation hotel, and uninfected healthy controls (HCs) from the community were prospectively recruited. Participants were recruited at Wuhan Union Hospital and underwent examinations, including quality-of-life evaluation (St. George Respiratory Questionnaire [SGRQ]), laboratory examination, chest computed tomography (CT) imaging, and pulmonary function tests. A total of 216 participants were recruited, including 95 patients who had recovered from severe/critical COVID-19 (SPs), 51 who had recovered from mild/moderate disease (MPs), 28 who had recovered from asymptomatic disease (APs), and 42 HCs. In total, 154 out of 174 (88.5%) recovered COVID-19 patients tested positive for serum SARS-COV-2 IgG, but only 19 (10.9%) were still positive for IgM. The SGRQ scores were highest in the SPs, while APs had slightly higher SGRQ scores than those of HCs; 85.1% of SPs and 68.0% of MPs still had residual CT abnormalities, mainly ground-glass opacity (GGO) followed by strip-like fibrosis at 3 months after discharge, but the pneumonic lesions were largely absorbed in the recovered SPs or MPs relative to findings in the acute phase. Pulmonary function showed that the frequency of lung diffusion capacity for carbon monoxide abnormalities were comparable in SPs and MPs (47.1 vs. 41.7%), while abnormal total lung capacity (TLC) and residual volume (RV) were more frequent in SPs than in MPs (TLC, 18.8 vs. 8.3%; RV, 11.8 vs. 0%). Pulmonary abnormalities remained after recovery from COVID-19 and were more frequent and conspicuous in SPs at 3 months after discharge.
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http://dx.doi.org/10.3389/fmed.2021.682087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270002PMC
June 2021

Inhibition of MEK5/ERK5 signaling overcomes acquired resistance to the third generation EGFR inhibitor, osimertinib, via enhancing Bim-dependent apoptosis.

Cancer Lett 2021 Jul 8;519:141-149. Epub 2021 Jul 8.

Department of Hematology and Medical Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA, USA. Electronic address:

The promising therapeutic efficacy of the third generation EGFR inhibitor, osimertinib (AZD9291), for the treatment of patients with EGFR-mutant non-small cell lung cancer (NSCLC) has been demonstrated in the clinic both as first-line and second line therapy. However, inevitable acquired resistance limits its long-term benefit to patients and is thus a significant clinical challenge. The current study focuses on studying the potential role of targeting MEK5-ERK5 signaling in overcoming acquired resistance to osimertinib. Osimertinib and other third generation EGFR inhibitors exerted a rapid and sustained suppressive effect on ERK5 phosphorylation primarily in EGFR-mutant NSCLC cell lines and lost this activity in some osimertinib-resistant cell lines. Osimertinib combined with either ERK5 or MEK5 inhibitors synergistically decreased the survival of osimertinib-resistant cell lines with enhanced induction of apoptosis primarily via augmenting Bim expression. Moreover, the combination effectively inhibited the growth of osimertinib-resistant xenografts in vivo. Together, these findings suggest the potential role of MEK5-ERK5 signaling in modulating development of acquired resistance to osimertinib and value of targeting this signaling as a potential strategy in overcoming acquired resistance to osimertinib and possibly other third generation EGFR inhibitors.
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http://dx.doi.org/10.1016/j.canlet.2021.07.007DOI Listing
July 2021

A synthetic circuit for buffering gene dosage variation between individual mammalian cells.

Nat Commun 2021 07 5;12(1):4132. Epub 2021 Jul 5.

Systems, Synthetic, and Physical Biology Program, Rice University, Houston, TX, USA.

Precise control of gene expression is critical for biological research and biotechnology. However, transient plasmid transfections in mammalian cells produce a wide distribution of copy numbers per cell, and consequently, high expression heterogeneity. Here, we report plasmid-based synthetic circuits - Equalizers - that buffer copy-number variation at the single-cell level. Equalizers couple a transcriptional negative feedback loop with post-transcriptional incoherent feedforward control. Computational modeling suggests that the combination of these two topologies enables Equalizers to operate over a wide range of plasmid copy numbers. We demonstrate experimentally that Equalizers outperform other gene dosage compensation topologies and produce as low cell-to-cell variation as chromosomally integrated genes. We also show that episome-encoded Equalizers enable the rapid generation of extrachromosomal cell lines with stable and uniform expression. Overall, Equalizers are simple and versatile devices for homogeneous gene expression and can facilitate the engineering of synthetic circuits that function reliably in every cell.
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http://dx.doi.org/10.1038/s41467-021-23889-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257781PMC
July 2021

Two new calix[4]resorcinarene-based coordination cages adjusted by metal ions for the Knoevenagel condensation reaction.

Dalton Trans 2021 Jul;50(28):9942-9948

Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education, Department of Chemistry, Northeast Normal University, Changchun 130024, China.

Two new calix[4]resorcinarene-based coordination cages, namely, [Zn4(TPC4R)(PDC)4]·2DMF·6H2O (1-Zn) and [In11(TPC4R)2(PDC)16(μ2-OH)2(H2O)2]·[(CH3)2NH2]·8DMF·20H2O·EtOH (2-In), have been synthesized via solvothermal reactions (TPC4R = tetra(2-(4H-pyrazol-3-yl)pyridine)calix[4]resorcinarene, H2PDC = 3,5-pyridinedicarboxylic acid, DMF = N,N'-dimethylformamide). By carefully tuning different metal ions, two structurally different cages 1-Zn and 2-In were achieved. The former shows a bowl-shaped structure, while the latter features a dumbbell-like structure. After activation, they exhibited unsaturated Zn(ii) or In(iii) Lewis acid sites and the free nitrogen Lewis base sites of the PDC2-. Therefore, they were employed as catalysts for the Knoevenagel condensation reaction in the absence of a solvent. Particularly, 1-Zn featured high structural stability and enhanced the catalytic activity.
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http://dx.doi.org/10.1039/d1dt01139aDOI Listing
July 2021

Pharmacological Activating Transcription Factor 6 Activation Is Beneficial for Liver Retrieval With Normothermic Mechanical Perfusion From Cardiac Dead Donor Rats.

Front Surg 2021 18;8:665260. Epub 2021 Jun 18.

Department of Hepatobiliary and Pancreatic Surgery, Zhengzhou Key Laboratory for HPB Diseases and Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.

Normothermic machine perfusion (NMP) could be beneficial for organ retrieval from donors after cardiac death (DCD). Activating transcription factor 6 (ATF6) was recently shown to mitigate liver ischemia/reperfusion injury and confer protection. The aims of this study were to assess the implication of ATF6 in liver retrieval from DCD rat livers with NMP and explore the effect of pharmacologic ATF-6 activation on liver retrieval. The livers from DCD rats were exposed to 30 min of warm ischemia and 8 h cold preservation followed by 2 h NMP with or without an ATF6 activator in the perfusate. Perfusates and livers were harvested to detect ATF6 expression, liver function, and inflammation. DCD livers with NMP were associated with ATF6 overexpression and activation based on IHC and WB ( < 0.05). The ATF6 activator downregulated perfusate aminotransferases, decreased the Suzuki score, downregulated CD68 and MPO based on IHC, induced the expression of cytochrome c in mitochondria and inhibited the expression of cytochrome c in cytoplasm based on WB, reduced TNFα and IL-6 levels based on ELISA, decreased levels of MDA, GSSG and ATP, and increased SOD activity and GSH levels in the perfused livers ( < 0.05). ATF6 is important for liver retrieval, and an exogenous ATF6 activator accelerates liver retrieval from DCD rats in an NMP model.
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http://dx.doi.org/10.3389/fsurg.2021.665260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249577PMC
June 2021

Efficient Preparation of Chitooligosaccharide With a Potential Chitosanase Csn-SH and Its Application for Fungi Disease Protection.

Front Microbiol 2021 17;12:682829. Epub 2021 Jun 17.

College of Natural Resources and Environment, South China Agricultural University, Guangzhou, China.

Chitosanase plays a vital role in bioactive chitooligosaccharide preparation. Here, we characterized and prepared a potential GH46 family chitosanase from BSS. The purified recombinant enzyme Csn-SH showed a molecular weight of 27.0 kDa. Csn-SH displayed maximal activity toward chitosan at pH 5.0 and 45°C. Thin-layer chromatography and electrospray ionization-mass spectrometry indicated that Csn-SH mainly hydrolyzed chitosan into (GlcN), (GlcN), and (GlcN) with an endo-type cleavage pattern. Molecular docking analysis demonstrated that Csn-SH cleaved the glycoside bonds between subsites -2 and + 1 of (GlcN). Importantly, the chitosan hydrolysis rate of Csn-SH reached 80.57% within 40 min, which could reduce time and water consumption. The hydrolysates prepared with Csn-SH exhibited a good antifungal activity against and . The above results suggested that Csn-SH could be used to produce active chitooligosaccharides efficiently that are biocontrol agents applicable for safe and sustainable agricultural production.
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http://dx.doi.org/10.3389/fmicb.2021.682829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249199PMC
June 2021

Functional analysis of deleterious SNPs in lens epithelial cells.

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

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

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

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

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

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

Application of an appendoscope in chronic appendicitis.

Endoscopy 2021 Jul 2. Epub 2021 Jul 2.

Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

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http://dx.doi.org/10.1055/a-1519-6903DOI Listing
July 2021

Astaxanthin Protects Dendritic Cells from Lipopolysaccharide-Induced Immune Dysfunction.

Mar Drugs 2021 Jun 17;19(6). Epub 2021 Jun 17.

College of Food Science and Engineering, Yangzhou University, Yangzhou 225009, China.

Astaxanthin, originating from seafood, is a naturally occurring red carotenoid pigment. Previous studies have focused on its antioxidant properties; however, whether astaxanthin possesses a desired anti-inflammatory characteristic to regulate the dendritic cells (DCs) for sepsis therapy remains unknown. Here, we explored the effects of astaxanthin on the immune functions of murine DCs. Our results showed that astaxanthin reduced the expressions of LPS-induced inflammatory cytokines (TNF-α, IL-6, and IL-10) and phenotypic markers (MHCII, CD40, CD80, and CD86) by DCs. Moreover, astaxanthin promoted the endocytosis levels in LPS-treated DCs, and hindered the LPS-induced migration of DCs via downregulating CCR7 expression, and then abrogated allogeneic T cell proliferation. Furthermore, we found that astaxanthin inhibited the immune dysfunction of DCs induced by LPS via the activation of the HO-1/Nrf2 axis. Finally, astaxanthin with oral administration remarkably enhanced the survival rate of LPS-challenged mice. These data showed a new approach of astaxanthin for potential sepsis treatment through avoiding the immune dysfunction of DCs.
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http://dx.doi.org/10.3390/md19060346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235365PMC
June 2021
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