Publications by authors named "Li Sun"

2,135 Publications

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WRKY46 promotes ammonium tolerance in Arabidopsis by repressing NUDX9 and IAA-conjugating genes and by inhibiting NH efflux in the root elongation zone.

New Phytol 2021 Jun 15. Epub 2021 Jun 15.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing, 210008, China.

Ammonium (NH ) is toxic to root growth in most plants already at moderate levels. Transcriptional regulation is one of the most important mechanisms in plant's response to NH toxicity, but the nature of the involvement of transcription factors (TFs) in this regulation remains unclear. Here, RNA-seq analysis in Arabidopsis roots was performed to screen ammonium-responsive TFs. WRKY46, the member of the WRKY transcription factor family most responsive to NH , was selected. We define the role of WRKY46 by using mutation and overexpression assays, and characterize the regulation of NUDX9 and IAA-conjugating genes by WRKY46 via yeast one-hybrid and electrophoretic mobility shift assays and ChIP-quantitative PCR. Knockout of WRKY46 increased, while overexpression of WRKY46 decreased, NH -suppression of the primary root. WRKY46 is shown to directly bind to the promoters of the NUDX9 and IAA-conjugating genes (GH3.1, GH3.6, UGT75D1, UGT84B2) and inhibits their transcription, thus positively regulating free IAA content and stabilizing protein N-glycosylation, leading to an inhibition of NH efflux in the root elongation zone (EZ). We identify TF involvement in regulating NH efflux in the EZ, and show that WRKY46 inhibits NH efflux by negative regulation of NUDX9 and IAA-conjugating genes.
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http://dx.doi.org/10.1111/nph.17554DOI Listing
June 2021

Multiplex protein profiling method for extracellular vesicle protein detection.

Sci Rep 2021 Jun 14;11(1):12477. Epub 2021 Jun 14.

Department of Biomedical Sciences, Florida State University College of Medicine, 1115 W. Call Street, Tallahassee, FL, 32306-4300, USA.

Extracellular vesicles (EVs) are small nanometer-sized membrane sacs secreted into biological fluids by all cells. EVs encapsulate proteins, RNAs and metabolites from its origin cell and play important roles in intercellular communication events. Over the past decade, EVs have become a new emerging source for cancer diagnostics. One of the challenges in the study of EVs and there utility as diagnostic biomarkers is the amount of EVs needed for traditional protein analysis methods. Here, we present a new immuno-PCR method that takes advantage of commercially available TotalSeq antibodies containing DNA conjugated oligos to identify immobilized protein analysts using real-time qPCR. Using this method, we demonstrate that multiple EV surface proteins can be profiled simultaneously with high sensitivity and specificity. This approach was also successfully applied to similar protocol using cell and serum samples. We further described the development of a micro-size exclusion chromatography method, where we were able to detect EV surface proteins with as little as 10 μL of human serum when combined with immuno-PCR. Overall, these results show that the immuno-PCR method results in rapid detection of multiple EV markers from small sample volumes in a single tube.
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http://dx.doi.org/10.1038/s41598-021-92012-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203679PMC
June 2021

Overexpression of improves the tolerance of Arabidopsis to salt stress.

3 Biotech 2021 Jul 8;11(7):316. Epub 2021 Jun 8.

State Key Laboratory of Tree Genetics and Breeding (Northeast Forestry University), Harbin, 150040 People's Republic of China.

Alternative oxidase (AOX) has a well-established involvement in plant growth and stress tolerance in many studies. In this study, we isolated and characterized the AOX2 from . The Open Reading Frame (ORF) contains 1029 nucleotides and encodes 342 amino acid residues. The inferred amino acid sequence of shared the highest sequence similarity with a homolog from . The transcripts were relatively abundant in the old leaves and significantly up-regulated by salt stress. Subcellular localization analysis showed that was located in the mitochondria. We transformed into wild-type and found that compared with wild-type and mutant lines, heterotopic expression of increased proline content, and peroxidase and superoxide dismutase activities, while decreasing relative conductivity and the reactive oxygen species level. Further, the ratio of alternate respiration to the total respiration in plants that overexpressed was significantly higher than that in wild-type and mutant plants under salt stress. These results indicate that plays a key role in salt tolerance.
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http://dx.doi.org/10.1007/s13205-021-02871-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187684PMC
July 2021

Restriction of Iron Loading into Developing Seeds by A YABBY Transcription Factor Safeguards Successful Reproduction in Arabidopsis.

Mol Plant 2021 Jun 8. Epub 2021 Jun 8.

State Key Laboratory of Plant Physiology and Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou 310058, China;. Electronic address:

Iron (Fe) storage in plant seeds is not only necessary for seedling establishment following germination, but also a major source of dietary Fe for human and animal life. Seed Fe accumulation was known to be low during early seed development. However, the underlying mechanism and biological significance remain elusive. Here, we show that reduced expression of Arabidopsis YABBY transcription factor INNER NO OUTER (INO) increases embryonic Fe accumulation, while transgenic overexpression of INO has opposite effect. INO is highly expressed during early seed development, and that decreased expression of INO increases the expression of NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN 1 (NRAMP1), a gene encoding a transporter contributing to Fe loading into the seed. The relatively high embryonic Fe accumulation conferred by decreased expression of INO is rescued by the nramp1 loss-of-function mutation. We further demonstrate that INO represses NRAMP1 expression by binding to NRAMP1 specific promoter region. Moreover, we show that excessive Fe loading into developing seeds in ino mutants produces more oxidative damage, leading to increased cell death and seed abortion, a phenotype that can be rescued by nramp1 mutation. Taken together, these results indicate that INO plays an important role in safeguarding reproduction by reducing Fe loading into developing seeds via repression of NRAMP1 expression.
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http://dx.doi.org/10.1016/j.molp.2021.06.005DOI Listing
June 2021

Comprehensive Proteomic Profiling of Aqueous Humor Proteins in Proliferative Diabetic Retinopathy.

Transl Vis Sci Technol 2021 May;10(6)

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong Province, China.

Purpose: Proliferative diabetic retinopathy (PDR) is a serious ocular disease that can lead to retinal microvascular complications in patients with diabetes mellitus. To date, no studies have explored PDR development by analyzing the aqueous humor (AH). Therefore we carried out tandem mass tag (TMT) proteomic quantification to compare AH protein profiles between PDR and non-PDR subjects.

Methods: We enrolled six PDR and six control (senile cataract) subjects. AH samples were collected during surgery and stored at -80°C. Proteins were extracted, trypsin-digested, and labeled with TMTs for mass spectrometric analysis.

Results: We found 191 proteins to be changed with |log2 (fold change)| ≥1 (P < 0.05 and identification with at least two peptides per protein). Of them, 111 were downregulated, whereas 80 were upregulated in the PDR group. Proteomic bioinformatic analysis indicated that PDR development was related to complement and coagulation cascades, platelet activation, extracellular matrix-receptor interaction, focal adhesion, protein digestion and absorption, human papillomavirus infection, PI3K-Akt signaling pathway, cholesterol metabolism, peroxisome proliferator-activated receptor signaling pathways, fat digestion and absorption, and vitamin digestion and absorption pathways.

Conclusions: Comprehensive proteomic profiling of the AH revealed 191 differentially expressed proteins between the two groups. Most of these proteins belong to secretory pathways, and therefore can be used as biomarkers in clinical testing and basic research.

Translational Relevance: Pathway analysis and a review of the literature enabled us to draw a novel biological map that will support further studies on the underlying mechanisms and therapeutic control of PDR development.
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http://dx.doi.org/10.1167/tvst.10.6.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107506PMC
May 2021

STING inhibitors target the cyclic dinucleotide binding pocket.

Proc Natl Acad Sci U S A 2021 Jun;118(24)

State Key Laboratory of Natural Medicines, Department of Life Science and Technology, China Pharmaceutical University, 211198 Nanjing, China;

Cytosolic DNA activates cGAS (cytosolic DNA sensor cyclic AMP-GMP synthase)-STING (stimulator of interferon genes) signaling, which triggers interferon and inflammatory responses that help defend against microbial infection and cancer. However, aberrant cytosolic self-DNA in Aicardi-Goutière's syndrome and constituently active gain-of-function mutations in STING in STING-associated vasculopathy with onset in infancy (SAVI) patients lead to excessive type I interferons and proinflammatory cytokines, which cause difficult-to-treat and sometimes fatal autoimmune disease. Here, in silico docking identified a potent STING antagonist SN-011 that binds with higher affinity to the cyclic dinucleotide (CDN)-binding pocket of STING than endogenous 2'3'-cGAMP. SN-011 locks STING in an open inactive conformation, which inhibits interferon and inflammatory cytokine induction activated by 2'3'-cGAMP, herpes simplex virus type 1 infection, deficiency, overexpression of cGAS-STING, or SAVI STING mutants. In mice, SN-011 was well tolerated, strongly inhibited hallmarks of inflammation and autoimmunity disease, and prevented death. Thus, a specific STING inhibitor that binds to the STING CDN-binding pocket is a promising lead compound for STING-driven disease.
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http://dx.doi.org/10.1073/pnas.2105465118DOI Listing
June 2021

A case report of infantile parkinsonism-dystonia-2 caused by homozygous mutation in the gene.

Int J Neurosci 2021 Jun 2:1-4. Epub 2021 Jun 2.

Rehabilitation and Treatment Centre for Cerebral Palsy, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.

A 6-month-old male infant who presented with developmental delay and suspected cerebral palsy was diagnosed with infantile parkinsonism-dystonia-2 (MIM: 618049). The whole-exome sequencing identified a homozygous c.710C > T (p.Pro237His) transition in the monoamine transporter gene , which was due to paternal uniparental disomy (UPD) of chromosome 10p15.3q26.3, resulting in brain dopamine-serotonin vesicular transport disease. Sanger sequencing confirmed that his unaffected father carried the same mutation in the heterozygous state, while his mother did not carry the same mutation. Autosomal recessive gene mutations in has been identified in three families in different countries. The infant was treated with pramipexole, a dopamine agonist, and the static tremor was better compared with that before treatment, but the movement disorder was not significantly improved. This case confirmed the causal mutation of gene and brain dopamine-serotonin vesicular transport disease, which suggested the mechanism of UPD homozygous formation, and confirmed that dopamine agonist treatment could improve some symptoms in affected individuals.
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http://dx.doi.org/10.1080/00207454.2021.1938036DOI Listing
June 2021

C118P, a novel microtubule inhibitor with anti-angiogenic and vascular disrupting activities, exerts anti-tumor effects against hepatocellular carcinoma.

Biochem Pharmacol 2021 May 30;190:114641. Epub 2021 May 30.

Department of Pharmacy, Zhuhai People's Hospital (Zhuhai Hospital affiliated with Jinan University), Zhuhai 519000 China. Electronic address:

Hepatocellular carcinoma (HCC), a hypervascular solid tumor, is the most leading cause of cancer mortality worldwide. Microtubule binding agents targeting tumor vasculature have been investigated and employed clinically. C118P is a newly synthesized analog of CA4 with improved water solubility and extended half-life. The current studies investigated the pharmacological effects of C118P and its active metabolite C118. Here, we first confirmed by in vitro assays that C118 exerts microtubule depolymerization activity and by molecular docking revealed that it fits to the colchicine binding site of tubulin. In addition, we found that C118P and C118 altered microtubule dynamics and cytoskeleton in human umbilical vein endothelial cells. Accordingly, we observed that C118P and C118 inhibited angiogenesis and disrupted established vascular networks using tube formation assays and chick chorioallantoic membrane angiogenesis assays. In addition, our data showed that C118P and C118 exhibited board anti-proliferative effect on various cancer cells, including HCC cell lines, in MTT assays or Sulforhodamine B assays. Moreover, we found that C118P induced G2/M phase cell cycle arrest and apoptosis in HCC cell lines BEL7402 and SMMC7721 using flow cytometry analysis and immunoblotting assays. Finally, we confirmed that C118P suppressed HCC growth via targeting tumor vasculature and inducing apoptosis in the SMMC7721 xenograft mouse model. In conclusion, our studies revealed that C118P, as a potent microtubule destabilizing agent, exerts its multiple pharmacological effects against HCC by inducing cell cycle arrest and apoptosis, as well as targeting tumor vasculature. Thus, C118P might be a promising drug candidate for liver cancer treatment.
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http://dx.doi.org/10.1016/j.bcp.2021.114641DOI Listing
May 2021

Neural response to trauma-related and trauma-unrelated negative stimuli in remitted and persistent pediatric post-traumatic stress disorder.

Brain Behav 2021 Jun 2:e02173. Epub 2021 Jun 2.

Sixth Hospital/Institute of Mental Health, Peking University, Beijing, China.

Introduction: Most youths who suffer from post-traumatic stress disorder (PTSD) lose their diagnosis in the first 1-2 years. However, there are few studies on this brain mechanism, and the heterogeneity of the findings is partially due to the different stimuli applied and the mixed trauma history. Therefore, the use of trauma-related/unrelated stimuli to study the remittance mechanism of earthquake-induced PTSD could advance our knowledge of PTSD and inspire future treatment.

Methods: Thirteen youths with PTSD, 18 remitted participants, and 18 control participants underwent functional magnetic resonance imaging (fMRI), while viewing trauma-related pictures, trauma-unrelated negative pictures, and scrambled pictures.

Results: Under trauma-unrelated condition, the neural activity of the left hippocampus in the remitted group was between the two other groups. Under trauma-related condition, the PTSD and the remitted group exhibited higher neural activity in the right middle occipital gyrus than controls. The remitted group showed higher neural activity in the right parahippocampal gyrus and right lingual gyrus under trauma-related condition than trauma-unrelated condition, while no significant difference was found in PTSD group.

Conclusion: PTSD status-related group differences are mainly reflected in the left hippocampus under the trauma-unrelated condition, while the hyperactivity in the right middle occipital gyrus under trauma-related condition could be an endophenotype for PTSD.
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http://dx.doi.org/10.1002/brb3.2173DOI Listing
June 2021

Whey protein preloading can alleviate stress adaptation disorder and improve hyperglycemia in women with gestational diabetes mellitus.

Gynecol Endocrinol 2021 Jun 1:1-5. Epub 2021 Jun 1.

Department of Obstetrics and Gynecology, Yuhuangding Hospital Affiliated to Qingdao University, Yantai, China.

Aims: To investigate the change of stress hormones, oxidative stress and insulin resistance (IR) in women with gestational diabetes mellitus (GDM) after supplement whey protein, in an attempt to gain insights into the prevention and treatment of GDM.

Materials And Methods: 60 GDM women were recruited in this study, and 30 women received a preload drink containing 20 g whey protein as group GDM-W, and the other 30 women received control flavoring drink as group GDM, and the trial lasted for 14 days. Plasma epinephrine (E), noradrenaline (NE), and cortisol were detected; we also determined levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH). Homeostasis model assessment of insulin resistance (HOMA-IR) was used to assess IR.

Results: In the GDM-W group, postprandial blood glucose was decreased significantly on 3, 5, 7, and 14 days (all  < .05), plasma 2 h insulin was increased by 7.2, 8.6, and 20.5% on days 5, 7, and 14 ( < .05, .05, .01). HOMA-IR was decreased significantly on day 14 ( < .05). MDA was decreased by 20.7% on day 14 ( < .01), and anti-oxidative enzymes' SOD was decreased by 13.4% on day 14 ( < .05) and GSH was decreased by 16.7 and 29.1% on days 7 and 14 (both  < .05). Stress hormones E and cortisol were decreased by 10.8 and 19.8%, respectively, on day 14 ( < .05). There was no significant difference in NE between the two groups within 14 days.

Conclusions: Whey protein supplementation may improve hyperglycemia by alleviating stress disorder and oxidative stress injury in GDM women. This trial was registered at chictr.org.cn/as ChiCTR1800020413.
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http://dx.doi.org/10.1080/09513590.2021.1932803DOI Listing
June 2021

Donepezil prevents morphine tolerance by regulating N-methyl-d-aspartate receptor, protein kinase C and CaM-dependent kinase II expression in rats.

Pharmacol Biochem Behav 2021 Jul 28;206:173209. Epub 2021 May 28.

Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, China; Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.113 Baohe Road, Longgang District, Shenzhen 518116, China. Electronic address:

Current studies have indicated that donepezil as a cholinesterase inhibitor can attenuate morphine-induced tolerance. The present study aimed to evaluate the possible role of N-methyl-d-aspartate receptors (NMDARs), protein kinase C (PKC) and CaM-dependent kinase II (CaMKII) pathways in this effect. Female Wistar rats received daily morphine (10 mg/kg, i.p.) alone or in combination with donepezil (1.5 or 2 mg/kg, gavaged) for 14 days. The analgesic effect was assessed by Von-frey, hotplate and tail flick test. On the 15th day, the periaqueductal gray (PAG) and lumbar spinal cord of rats were dissected. Then, protein levels of NMDAR-NR1, NR2B, PKCγ and CaMKIIα were tested using Western blot method. The results showed that morphine tolerance was seen after 8-10 days of injection compared with control group, while daily co-administration of donepezil with morphine prolonged the occurrence of analgesic tolerance. Western blot showed that morphine significantly increased NR1, PKCγ and CaMKIIα expressions in PAG, and significantly increased PKCγ and CaMKIIα in spinal cord. In contrast, donepezil downregulated NR1 and PKCγ in PAG, and downregulated PKCγ and CaMKIIα in spinal cord. Moreover, donepezil alone activates NR1 and NR2B in spinal cord, which needs to be further studied. Thus, the present results suggest that the attenuation effects of donepezil on morphine tolerance are possibly mediated by preventing morphine-induced upregulations in NR1, PKCγ and CaMKIIα expressions.
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http://dx.doi.org/10.1016/j.pbb.2021.173209DOI Listing
July 2021

A natural variation of an SVP MADS-box transcription factor in Triticum petropavlovskyi leads to its ectopic expression and contributes to elongated glume.

Mol Plant 2021 May 25. Epub 2021 May 25.

State Key Laboratory of Crop Genetics and Germplasm Enhancement, Cytogenetics Institute, Nanjing Agricultural University/JCIC-MCP, Nanjing, Jiangsu 210095, China.

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http://dx.doi.org/10.1016/j.molp.2021.05.022DOI Listing
May 2021

Three Pb(COO) Cluster Frameworks Based on a Flexible Triazinetricarboxylic Acid Ligand: Syntheses, Structures, and Fluorescent Sensing Application for Nitrophenols.

Inorg Chem 2021 Jun 23;60(11):7887-7899. Epub 2021 May 23.

College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, P. R. China.

Three new metal-organic frameworks (MOFs), namely, [Pb(TTPCA)Cl]·3HO (), [Pb(TTPCA)(DMA)(HCOO)]·HO (), and [Pb(TTPCA)]·3DMF·2HO·HO (), were synthesized by the HTTPCA ligand [HTTPCA = 1,1',1″-(1,3,5-triazine-2,4,6-triyl)-tripiperidine-4-carboxylic acid], with lead(II) nitrate under solvothermal conditions. They were characterized by CHN analysis, IR spectroscopy, UV-vis spectroscopy, and single-crystal and powder X-ray diffraction. In addition, their thermogravimetric analysis and fluorescence properties were studied. Compounds - were 3D MOF structures with different Pb(COO) clusters: ([Pb(COO)Cl]), ([Pb(COO)]), and [Pb(COO)]. Fluorescence detection of compounds - shows that they can act as excellent sensors of nitrophenols with a low limit of detection and a high quenching constant.
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http://dx.doi.org/10.1021/acs.inorgchem.1c00408DOI Listing
June 2021

Targeting GLS1 to cancer therapy through glutamine metabolism.

Clin Transl Oncol 2021 May 23. Epub 2021 May 23.

Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated With Jinan University, Jinan University, Zhuhai, 519000, Guangdong, China.

Glutamine metabolism is one of the hallmarks of cancers which is described as an essential role in serving as a major energy and building blocks supply to cell proliferation in cancer cells. Many malignant tumor cells always display glutamine addiction. The "kidney-type" glutaminase (GLS1) is a metabolism enzyme which plays a significant part in glutaminolysis. Interestingly, GLS1 is often overexpressed in highly proliferative cancer cells to fulfill enhanced glutamine demand. So far, GLS1 has been proved to be a significant target during the carcinogenesis process, and emerging evidence reveals that its inhibitors could provide a benefit strategy for cancer therapy. Herein, we summarize the prognostic value of GLS1 in multiple cancer type and its related regulatory factors which are associated with antitumor activity. Moreover, this review article highlights the remarkable reform of discovery and development for GLS1 inhibitors. On the basis of case studies, our perspectives for targeting GLS1 and development of GLS1 antagonist are discussed in the final part.
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http://dx.doi.org/10.1007/s12094-021-02645-2DOI Listing
May 2021

Phosphorylated α-synuclein and phosphorylated tau-protein in sural nerves may contribute to differentiate Parkinson's disease from multiple system atrophy and progressive supranuclear paralysis.

Neurosci Lett 2021 Jun 19;756:135964. Epub 2021 May 19.

Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. Electronic address:

Differential diagnosis of Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear paralysis (PSP) is challenging. This study aimed to investigate the expression of phosphorylated α-synuclein (p-α-syn) and phosphorylated tau-protein (p-tau) in sural nerves from patients with PD, MSA and PSP to find biomarkers for differential diagnosis. Clinical evaluations and sural nerve biopsies were performed on 8 PD patients, 8 MSA patients, 6 PSP patients and 8 controls (CTRs). Toluidine blue staining was used to observe morphological changes in sural nerves. The deposition of p-α-syn and p-tau was detected by immunohistochemistry with semiquantitative evaluation. Locations of p-α-syn and p-tau were identified by double immunofluorescent staining. In case groups, the density of nerve fibres decreased with swollen or fragmented Schwann cells (SCs). All cases (22/22) but no CTRs (0/8) presented p-α-syn immunoreactivity with gradually decreasing semiquantitative levels among the PD (6.00 ± 2.07), MSA (5.00 ± 2.33) and PSP (3.50 ± 1.52) groups. p-tau aggregates were found in 7/8 MSA (1.88 ± 1.46) and 6/6 PSP (1.67 ± 0.52) patients but not in PD patients or CTRs. There were different expression patterns of p-α-syn and p-tau in PD, MSA and PSP patients. These findings suggest that peripheral sensory nerve injury exists in PD, MSA and PSP patients. With a different expression pattern and level, p-α-syn and p-tau in sural nerves may serve as novel biomarkers for differential diagnosis of PD, MSA and PSP.
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http://dx.doi.org/10.1016/j.neulet.2021.135964DOI Listing
June 2021

A virulent strain from deep-sea cold seep induces pyroptosis in a manner that involves NLRP3 inflammasome, JNK pathway, and lysosomal rupture.

Virulence 2021 Dec;12(1):1362-1376

Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, China.

Recent studies indicate that the species is distributed in deep-sea environments. However, no specific studies on deep-sea have been documented. In the present work, we isolated a strain, H2, from the deep-sea cold seep in South China Sea. We characterized the pathogenic potential of H2 and investigated H2-induced death of different types of cells. We found that H2 was capable of tissue dissemination and causing acute mortality in mice and fish following intraperitoneal/intramuscular injection. studies revealed that H2 infection of macrophages induced pyroptosis and activation of the NLRP3 inflammasome pathway that contributed partly to cell death. H2 infection activated p38, JNK, and ERK, but only JNK proved to participate in H2-triggered cell death. Reactive oxygen species (ROS) and intracellular Ca were essential to H2-induced activation of JNK and NLRP3 inflammasome. In contrast, lysosomal rupture and cathepsins were required for H2-induced NLRP3 inflammasome activation but not for JNK activation. This study revealed for the first time the virulence characteristics of deep-sea and provided new insights into the mechanism of infection.
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http://dx.doi.org/10.1080/21505594.2021.1926649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143241PMC
December 2021

Epidermal Growth Factor Receptor Mutation Mechanisms in Nonsmall Cell Lung Cancer by Transcriptome Sequencing.

Cancer Biother Radiopharm 2021 May 18. Epub 2021 May 18.

Department of Elderly Respiratory Medicine, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.

This study intended to investigate the mechanisms underlying the epidermal growth factor receptor (EGFR) mutations in nonsmall cell lung cancer (NSCLC). Lung cancer tissue samples were collected from 20 patients with NSCLC (6 EGFR mutation types assigned into 2 categories and 14 EGFR wild types assigned to 4 categories). The samples were subjected to transcriptome sequencing, followed by identification of the differentially expressed mRNAs (DEMs), differentially expressed lncRNAs (DELs), and differentially expressed circRNAs (DECs) between the mutation and nonmutation groups. Function analysis and microRNA (miRNA) prediction for DEMs were performed. The correlations between long noncoding RNA (lncRNA)/circular RNA (circRNA) and messenger RNA (mRNA) were analyzed. In addition, the targeting lncRNA and circRNA of miRNA were predicted. Finally, competing endogenous RNA (ceRNA) network was constructed, and survival analysis for the mRNAs involved in the network was performed. In total, 323 DEMs, 284 DELs, and 224 DECs were identified between EGFR mutation and nonmutation groups. The DEMs were significantly involved in gene ontology functions related to cilium morphogenesis and assembly. ceRNA networks were constructed based on the DEMs, DELs, DECs, and predicted miRNAs. Survival analysis showed that four genes in the ceRNA network, including , , , and , were significantly associated with prognosis. The four genes were involved in several ceRNA pathways, including RP1-191J18/circ_000373/miR-520a-5p/, RP5-1014D13/let-7i-5p/, circ_000373/miR-1293/, and RP1-191J18/circ_000373/miR-378a-5p/. EGFR mutations in NSCLC may be associated with cilium dysfunction and complex ceRNA regulatory mechanisms. The key RNAs in the ceRNA network may be used as promising biomarkers for predicting EGFR mutations in NSCLC.
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http://dx.doi.org/10.1089/cbr.2020.4049DOI Listing
May 2021

The Cross-Link between Ferroptosis and Kidney Diseases.

Oxid Med Cell Longev 2021 3;2021:6654887. Epub 2021 May 3.

Department of Nephrology, The First Affiliated Hospital of China Medical University, Shenyang, 110000 Liaoning Province, China.

Acute and chronic kidney injuries result from structural dysfunction and metabolic disorders of the kidney in various etiologies, which significantly affect human survival and social wealth. Nephropathies are often accompanied by various forms of cell death and complex microenvironments. In recent decades, the study of kidney diseases and the traditional forms of cell death have improved. Nontraditional forms of cell death, represented by ferroptosis and necroptosis, have been discovered in the field of kidney diseases, which have reshuffled the role of traditional cell death in nephropathies. Although interactions between ferroptosis and acute kidney injury (AKI) have been continuously explored, studies on ferroptosis and chronic kidney disease (CKD) remain limited. Here, we have reviewed the therapeutic significance of ferroptosis in AKI and anticipated the curative potential of ferroptosis for CKD in the hope of providing insights into ferroptosis and CKD.
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http://dx.doi.org/10.1155/2021/6654887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110383PMC
May 2021

Detection of circRNA Biomarker for Acute Myocardial Infarction Based on System Biological Analysis of RNA Expression.

Front Genet 2021 30;12:686116. Epub 2021 Apr 30.

Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin, China.

Acute myocardial infarction (AMI) is myocardial necrosis caused by the persistent interruption of myocardial blood supply, which has high incidence rate and high mortality in middle-aged and elderly people in the worldwide. Biomarkers play an important role in the early diagnosis and treatment of AMI. Recently, more and more researches confirmed that circRNA may be a potential diagnostic biomarker and therapeutic target for cardiovascular diseases. In this paper, a series of biological analyses were performed to find new effective circRNA biomarkers for AMI. Firstly, the expression levels of circRNAs in blood samples of patients with AMI and those with mild coronary stenosis were compared to reveal circRNAs which were involved in AMI. Then, circRNAs which were significant expressed abnormally in the blood samples of patients with AMI were selected from those circRNAs. Next, a ceRNA network was constructed based on interactions of circRNA, miRNA and mRNA through biological analyses to detect crucial circRNA associated with AMI. Finally, one circRNA was selected as candidate biomarker for AMI. To validate effectivity and efficiency of the candidate biomarker, fluorescence in situ hybridization, hypoxia model of human cardiomyocytes, and knockdown and overexpression analyses were performed on candidate circRNA biomarker. In conclusion, experimental results demonstrated that the candidate circRNA was an effective biomarker for diagnosis and therapy of AMI.
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http://dx.doi.org/10.3389/fgene.2021.686116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120315PMC
April 2021

Bile Acids Elevated in Chronic Periaortitis Could Activate Farnesoid-X-Receptor to Suppress IL-6 Production by Macrophages.

Front Immunol 2021 22;12:632864. Epub 2021 Apr 22.

Department of Rheumatology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Chronic periaortitis (CP) is a rare autoimmune disease without effective treatment. By analyzing the serum bile acid spectrum in 28 CP patients with the ultra-performance liquid chromatography-tandem mass spectrometry, we found that the bile acids were significantly altered in CP patients, with significant increases in chenodeoxycholic acid (CDCA) and glycochenodeoxycholic acid (GCDCA) and decrease in deoxycholic acid (DCA). Signaling pathway enrichment analysis from the RNA sequencing results suggested that the altered gene sets in PBMC of CP patients were associated with bile acid metabolism. Furthermore, we found that pathological concentration of CDCA could significantly inhibited IL-6 expression in RAW 264.7 cells after LPS stimulation. Since CDCA is a well-known natural high-affinity ligand for the bile acid receptor farnesoid-x-receptor (FXR) while GW4064 is the synthetic specific agonist of this receptor, we then revealed that GW4064 significantly decreased IL-6 expression in RAW 264.7 cells and bone marrow-derived macrophages but not in FXR macrophages upon LPS stimulation. The western blot results with the anti-FXR antibody showed significantly increased expression in the nuclear proportion, suggesting that FXR agonist promoted the transportation of FXR into the nucleus but did not increase the FXR expression in macrophages. Dual-luciferase report assay and ChIP assay demonstrated that upon activation, FXR could directly bind to the promoter site of IL-6, leading to the decreased expression of IL-6. Thus, bile acids, especially CDCA, may operate to damp inflammation FXR-mediated downregulation of IL-6 in mononuclear cells and provide a protective mechanism for CP patients.
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http://dx.doi.org/10.3389/fimmu.2021.632864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100322PMC
April 2021

Pathogenic Functions of Tumor Necrosis Factor Receptor- Factor 6 Signaling Traumatic Brain Injury.

Front Mol Neurosci 2021 21;14:629910. Epub 2021 Apr 21.

Department of Rehabilitation Medicine, Affiliated Hospital of Nantong University, Nantong, China.

Neuroinflammation contributes to delayed (secondary) neurodegeneration following traumatic brain injury (TBI). Tumor necrosis factor receptor-associated factor 6 (TRAF6) signaling may promote post-TBI neuroinflammation, thereby exacerbating secondary injury. This study investigated the pathogenic functions of TRAF6 signaling following TBI and . A rat TBI model was established by air pressure contusion while lipopolysaccharide (LPS) exposure was used to induce inflammatory-like responses in cultured astrocytes. Model rats were examined for cell-specific expression of TRAF6, NF-κB, phosphorylated (p)-NF-κB, MAPKs (ERK, JNK, and p38), p-MAPKs, chemokines (CCL2 and CXCL1), and chemokine receptors (CCR2 and CXCR2) by immunofluorescence, RT-qPCR, western blotting, and ELISA, for apoptosis by TUNEL staining, and spatial cognition by Morris water maze testing. These measurements were compared between TBI model rats receiving intracerebral injections of TRAF6-targeted RNAi vector (AAV9-TRAF6-RNAi), empty vector, MAPK/NF-κB inhibitors, or vehicle. Primary astrocytes were stimulated with LPS following TRAF6 siRNA or control transfection, and NF-κB, MAPKs, chemokine, and chemokine receptor expression levels evaluated by western blotting and ELISA. TRAF6 was expressed mainly in astrocytes and neurons of injured cortex, peaking 3 days post-TBI. Knockdown by AAV9-TRAF6-RNAi improved spatial learning and memory, decreased TUNEL-positive cell number in injured cortex, and downregulated expression levels of p-NF-κB, p-ERK, p-JNK, p-p38, CCL2, CCR2, CXCL1, and CXCR2 post-TBI. Inhibitors of NF-κB, ERK, JNK, and p38 significantly suppressed CCL2, CCR2, CXCL1, and CXCR2 expression following TBI. Furthermore, TRAF6-siRNA inhibited LPS-induced NF-κB, ERK, JNK, p38, CCL2, and CXCL1 upregulation in cultured astrocytes. Targeting TRAF6-MAPKs/NF-κB-chemokine signaling pathways may provide a novel therapeutic approach for reducing post-TBI neuroinflammation and concomitant secondary injury.
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http://dx.doi.org/10.3389/fnmol.2021.629910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096983PMC
April 2021

Prenatal diagnosis of familial recessive PIGN mutation associated with multiple anomalies: A case report.

Taiwan J Obstet Gynecol 2021 May;60(3):530-533

Center of Prenatal Diagnosis, Women and Children's Hospital Affiliated to Xiamen University, PR China. Electronic address:

Objective: We present a novel homozygous splice site mutation in the PIGN gene identified by whole exome sequencing and explored the genotype-phenotype correlation.

Case Report: A healthy 32-year-old woman underwent an ultrasound at 13 + 5 weeks of gestation. The ultrasound revealed multiple anomalies again including cystic hygroma, omphalocele and a ventricular septal defect. The pregnancy was subsequently terminated, and whole exome sequencing revealed a novel homozygous splice site mutation in the PIGN gene c.963 G > A (p.Gln321Gln). The same variant was also detected by pedigree-based Sanger sequencing in both parents as heterozygous, while they had normal karyotypes.

Conclusion: Our case report enhances the phenotype-genotype correlation associated with homozygous loss of function mutations in the PIGN gene.
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http://dx.doi.org/10.1016/j.tjog.2021.03.026DOI Listing
May 2021

Long-term safety, efficacy, and tolerability of levetiracetam in pediatric patients with epilepsy in Uygur, China: A retrospective analysis.

Epilepsy Behav 2021 Jul 5;120:108010. Epub 2021 May 5.

Department of Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Province 830001, China; Institute of Clinical Pharmacy, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Province 830001, China. Electronic address:

Purpose: Levetiracetam is approved as an add-on therapy to treat refractory partial seizures in pediatric patients over four years old. The efficacy and safety in pediatric patients with epilepsy in Uygur, China, is unknown. Therefore, the objective of this study was to investigate the safety, efficacy, and tolerability of levetiracetam in pediatric patients with epilepsy in Uygur, China.

Methods: This retrospective study compared the efficacy and safety of levetiracetam monotherapy and in combination with other antiseizure medications (ASMs) in 1055 pediatric patients with epilepsy treated with levetiracetam. The seizure frequencies at 1, 2, and 3 years after starting levetiracetam therapy were recorded and compared with the baseline yearly frequency. Safety variables included the incidence and type of adverse reactions.

Results: A total of 680 (64%) pediatric patients responded to levetiracetam therapy with a more than 50% reduction in the frequency of seizures. Seizure-free rates increased over time, 13%, 15%, and 18% at 1, 2, and 3 years, respectively. The number of baseline ASMs and the order of levetiracetam introduction were highly significant, impacting the likelihood of seizure remission during a 3-year follow-up period (p < 0.001). During levetiracetam treatment, 233 pediatric patients (22%) experienced at least one adverse reaction.

Conclusion: These significant findings indicate that levetiracetam is likely to become a widely prescribed ASM for epilepsy in pediatric clinical practice because of its long-term safety, efficacy, and tolerability.
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http://dx.doi.org/10.1016/j.yebeh.2021.108010DOI Listing
July 2021

The comprehensive landscape of miR-34a in cancer research.

Cancer Metastasis Rev 2021 May 6. Epub 2021 May 6.

New Drug Screening Center, China Pharmaceutical University, Nanjing, 210009, China.

MicroRNA-34 (miR-34) plays central roles in human diseases, especially cancers. Inactivation of miR-34 is detected in cancer cell lines and tumor tissues versus normal controls, implying its potential tumor-suppressive effect. Clinically, miR-34 has been identified as promising prognostic indicators for various cancers. In fact, members of the miR-34 family, especially miR-34a, have been convincingly proved to affect almost the whole cancer progression process. Here, a total of 512 (miR-34a, 10/21), 85 (miR-34b, 10/16), and 114 (miR-34c, 10/14) putative targets of miR-34a/b/c are predicted by at least ten miRNA databases, respectively. These targets are further analyzed in gene ontology (GO), KEGG pathway, and the Reactome pathway dataset. The results suggest their involvement in the regulation of signal transduction, macromolecule metabolism, and protein modification. Also, the targets are implicated in critical signaling pathways, such as MAPK, Notch, Wnt, PI3K/AKT, p53, and Ras, as well as apoptosis, cell cycle, and EMT-related pathways. Moreover, the upstream regulators of miR-34a, mainly including transcription factors (TFs), lncRNAs, and DNA methylation, will be summarized. Meanwhile, the potential TF upstream of miR-34a/b/c will be predicted by PROMO, JASPAR, Animal TFDB 3.0, and GeneCard databases. Notably, miR-34a is an attractive target for certain cancers. In fact, miR-34a-based systemic delivery combined with chemotherapy or radiotherapy can more effectively control tumor progression. Collectively, this review will provide a panorama for miR-34a in cancer research.
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http://dx.doi.org/10.1007/s10555-021-09973-3DOI Listing
May 2021

Case Report: Histiocytic Necrotizing Lymphadenitis (Kikuchi-Fujimoto Disease) Concurrent With Aseptic Meningitis.

Front Neurol 2021 20;12:565387. Epub 2021 Apr 20.

Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, China.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare, benign, self-limiting disease characterized by local lymphadenopathy. Central nervous system involvement in KFD is extremely rare and remains a diagnostic challenge. Only 41 cases of aseptic meningitis associated with KFD have been reported worldwide, with just four cases (including our case) of KFD with meningitis as the first symptom. We report a case of KFD accompanied by aseptic meningitis with severely high intracranial pressure (400 mmHO), increased white blood cell count (56 × 10/L), and moderately elevated protein level (0.52 g/L). This case is unique in the delayed appearance of lymphadenopathy. After 1 month of treatment with steroids, fever, headache, and lymphadenopathy gradually disappeared, and the result of cerebrospinal fluid examination gradually became normal. In conclusion, based on our case findings and our literature review on KFD with aseptic meningitis, a diagnosis of KFD should be considered when delayed appearance of lymphadenopathy is observed in patients with aseptic meningitis.
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http://dx.doi.org/10.3389/fneur.2021.565387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093430PMC
April 2021

Sparstolonin B exerts beneficial effects on prostate cancer by acting on the reactive oxygen species-mediated PI3K/AKT pathway.

J Cell Mol Med 2021 Jun 5;25(12):5511-5524. Epub 2021 May 5.

Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China.

Prostate cancer is a major health concern in males worldwide, owing to its high incidence. Sparstolonin B (SsnB), a component of the Chinese herbal medicine Sparganium stoloniferum, is used to treat many diseases. However, the effects and mechanisms of action of SsnB in prostate cancer have not yet been reported. In this study, we evaluated the effects of SsnB on cellular processes and tumour growth. In particular, we verified that SsnB could inhibit the proliferation, migration and invasion of prostate cancer cells and induce apoptosis by activating G2/M phase arrest in vitro based on a series of cytological experiments. In vivo, we found that SsnB could inhibit tumour growth in nude mouse xenograft models. We further confirmed that SsnB could repress the PI3K/AKT pathway by increasing reactive oxygen species (ROS) accumulation and oxidative stress. Collectively, SsnB inhibits tumour growth and induces apoptosis in prostate cancer via the suppression of the ROS-mediated PI3K/AKT pathway and may be a new alternative to adjuvant therapy for prostate cancer.
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http://dx.doi.org/10.1111/jcmm.16560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184693PMC
June 2021

Internalization of polystyrene microplastics in Euglena gracilis and its effects on the protozoan photosynthesis and motility.

Aquat Toxicol 2021 Jul 18;236:105840. Epub 2021 Apr 18.

College of Biological, Chemical Science and Engineering, Jiaxing University, Jiaxing 314001, P.R. China.

In this study, effects of polystyrene microplastics (MPS) on Euglena gracilis were investigated via examination on its photosynthesis and motility, two typical properties of the protozoan. No adverse effects were observed after 4-d exposure except for decrease in motility at two high MPS concentrations (5 and 25 mg/L). After 8-d duration, MPS at 1 mg/L had no obvious effects on E. gracilis, but two higher concentrations (5 and 25 mg/L) of MPS inhibited protozoan growth, motility, and photosynthesis. The reduced protozoan photosynthetic activity was reflected by changes in F/F (the maximum photochemical yield of PSII), ΔF (difference between F and F) and PI (the performance index), indicative of reduced quantum yield of electron transport and enhanced energy dissipation. A dose-dependent effect of MPS on E. gracilis was found in protozoan growth, photosynthesis and motility, especially photosynthetic indices. MPS of small size (75 nm) seemed more toxic to the protozoa than large size (1000 nm). Internalization of MPS in the cells and chloroplasts was observed clearly for the first time, likely responsible for their toxicity. Analysis on photosynthetic process and motility of E. gracilis could provide more comprehensive understanding of MPS toxicity in the aquatic environment, and may potentially serve as a biomonitoring tool.
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http://dx.doi.org/10.1016/j.aquatox.2021.105840DOI Listing
July 2021

Corrigendum to "Achieving reliable partial nitrification and anammox process using polyvinyl alcohol gel beads to treat low-strength ammonia wastewater" [Bioresour. Technol. 324 (2021) 124669].

Bioresour Technol 2021 Aug 30;334:125193. Epub 2021 Apr 30.

Department of Energy and Mineral Engineering and EMS Energy Institute, The Pennsylvania State University, University Park, PA 16802, USA. Electronic address:

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http://dx.doi.org/10.1016/j.biortech.2021.125193DOI Listing
August 2021

Analysis of Development Mechanism of Giant Cell Arteritis in Nude Mouse Model through Color Duplex Sonography and Computerized Tomography Nanocontrast Agent.

Biomed Res Int 2021 9;2021:6627925. Epub 2021 Apr 9.

Department of Ultrasound, The Second Affiliated Hospital of Dalian Medical University, Dalian 116031, China.

To explore the application value of color duplex sonography and enhanced computerized tomography (CT) inspection based on a nanocontrast agent in diagnosis and pathogenesis in giant cell arteritis (GCA), the GCA nude mouse model was constructed. In this study, 40 healthy male BalB/c nude mice aged 6-8 weeks were randomly divided into a control group (no model) and an experimental group (model), with 20 mice in each group, and the temporal artery tissue of GCA patients diagnosed as positive by temporal artery biopsy was implanted into nude mice to construct a GCA nude mouse model. Abdominal aortic biopsy and immunohistochemistry were used to verify the success of the GCA nude mouse model. All nude mice were subjected to color duplex sonography and enhanced CT examination based on a nanocontrast agent. At the same time, the basic indicators such as body weight, temperature, white blood cell (WBC), lymphocytes (LYM), hemoglobin (HGB), and platelet (PLT) were measured, and the protein expression levels of interleukin-6 (IL-6) and signal transducer and activator of transcription 3 (STAT3) were detected by immunohistochemistry. The results showed that the temporal artery wall of the nude mice in the experimental group thickened and the lumen was significantly narrowed, indicating that the cell arteritis model of nude mice was successfully constructed; ultrasound examination showed that the right superficial temporal artery vascular cavity narrowed, the blood flow signal changed like a filling defect around the periphery, and there was a low echo halo. CT examination showed that the left superficial temporal artery narrowed, and the inner diameter of the narrow segment of blood vessels changed like a bead. The body weight of nude mice in the experimental group decreased significantly after the modeling was completed ( < 0.05); after modeling, the body temperature of the nude mice in the experimental group increased significantly ( < 0.05); LYM and HGB values of nude mice in the experimental group were significantly lower than those in the control group ( < 0.05); the content of IL-6, STAT3, IL-6, and STAT3 proteins in the arterial tissue of nude mice in the experimental group was lower than that of the control group ( < 0.05), indicating that color duplex sonography and CT contrast agent technology can be used in the diagnosis and development mechanism research of GC.
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http://dx.doi.org/10.1155/2021/6627925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053047PMC
May 2021

Impaired ATG16L-Dependent Autophagy Promotes Renal Interstitial Fibrosis in Chronic Renal Graft Dysfunction Through Inducing EndMT by NF-κB Signal Pathway.

Front Immunol 2021 13;12:650424. Epub 2021 Apr 13.

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Chronic renal graft dysfunction (CAD) is caused by multiple factors, including glomerular sclerosis, inflammation, interstitial fibrosis and tubular atrophy (IF/TA). However, the most prominent elements of CAD are IF/TA. Our studies have confirmed that endothelial-mesenchymal transition (EndMT) is an important source to allograft IF/TA. The characteristic of EndMT is the loss of endothelial marker and the acquisition of mesenchymal or fibroblastic phenotypes. Autophagy is an intracellular degradation pathway that is regulated by autophagy-related proteins and plays a vital role in many fibrotic conditions. However, whether or not autophagy contributes to fibrosis of renal allograft and how such mechanism occurs still remains unclear. Autophagy related 16 like gene (ATG16L) is a critical autophagy-related gene (ARG) necessary for autophagosome formation. Here, we first analyzed kidney transplant patient tissues from Gene Expression Omnibus (GEO) datasets and 60 transplant patients from our center. Recipients with stable kidney function were defined as non-CAD group and all patients in CAD group were histopathologically diagnosed with CAD. Results showed that ATG16L, as one significant differential ARG, was less expressed in CAD group compared to the non-CAD group. Furthermore, we found there were less autophagosomes and autolysosomes in transplanted kidneys of CAD patients, and downregulation of autophagy is a poor prognostic factor. In vitro, we found out that the knockdown of ATG16L enhanced the process of EndMT in human renal glomerular endothelial cells (HRGECs). , the changes of EndMT and autophagic flux were then detected in rat renal transplant models of CAD. We demonstrated the occurrence of EndMT, and indicated that abundance of ATG16L was accompanied by the dynamic autophagic flux change along different stages of kidney transplantation. Mechanistically, knockdown of ATG16L, specifically in endothelial cells, reduced of NF-κB degradation and excreted inflammatory cytokines (IL-1β, IL-6 and TNF-α), which could facilitate EndMT. In conclusion, ATG16L-dependent autophagic flux causing by transplant showed progressive loss increase over time. Inflammatory cytokines from this process promoted EndMT, thereby leading to progression of CAD. ATG16L served as a negative regulator of EndMT and development of renal graft fibrosis, and autophagy can be explored as a potential therapeutic target for chronic renal graft dysfunction.
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http://dx.doi.org/10.3389/fimmu.2021.650424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076642PMC
April 2021