Publications by authors named "Juan Zeng"

68 Publications

Printable Zinc-Ion Hybrid Micro-Capacitors for Flexible Self-Powered Integrated Units.

Nanomicro Lett 2020 Nov 5;13(1):19. Epub 2020 Nov 5.

State Key Laboratory of Material Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China.

Wearable self-powered systems integrated with energy conversion and storage devices such as solar-charging power units arouse widespread concerns in scientific and industrial realms. However, their applications are hampered by the restrictions of unbefitting size matching between integrated modules, limited tolerance to the variation of input current, reliability, and safety issues. Herein, flexible solar-charging self-powered units based on printed Zn-ion hybrid micro-capacitor as the energy storage module is developed. Unique 3D micro-/nano-architecture of the biomass kelp-carbon combined with multivalent ion (Zn) storage endows the aqueous Zn-ion hybrid capacitor with high specific capacity (196.7 mAh g at 0.1 A g). By employing an in-plane asymmetric printing technique, the fabricated quasi-solid-state Zn-ion hybrid micro-capacitors exhibit high rate, long life and energy density up to 8.2 μWh cm. After integrating the micro-capacitor with organic solar cells, the derived self-powered system presents outstanding energy conversion/storage efficiency (η = 17.8%), solar-charging cyclic stability (95% after 100 cycles), wide current tolerance, and good mechanical flexibility. Such portable, wearable, and green integrated units offer new insights into design of advanced self-powered systems toward the goal of developing highly safe, economic, stable, and long-life smart wearable electronics.
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http://dx.doi.org/10.1007/s40820-020-00546-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187672PMC
November 2020

Niujiaodihuang Detoxify Decoction inhibits ferroptosis by enhancing glutathione synthesis in acute liver failure models.

J Ethnopharmacol 2021 Jun 12;279:114305. Epub 2021 Jun 12.

School of Pharmacy, Guangdong Medical University, Dongguan, 524023, China. Electronic address:

Ethnopharmacological Relevance: Niujiaodihuang Detoxify Decoction (NDD) is an integrated traditional Chinese medicine prescription that has been used as a therapeutic agent for the treatment of acute liver failure (ALF). However, the mechanisms underlying its action remain unclear.

Aim Of The Study: To determine the protective effect of NDD on D-galactosamine/lipopolysaccharide (D-GalN/LPS)-induced ALF and explore the underlying mechanisms.

Materials And Methods: We characterized the NDD fingerprint by HPLC and established D-GalN/LPS-induced ALF models in Sprague-Dawley rats and LO2 cells. Next, we measured the protective and antiferroptotic effects of NDD in vivo and in vitro. To further investigate the molecular mechanisms underlying the effects of NDD, we performed metabolomic analysis of the liver tissue using LC-MS/MS.

Results: Results of serum biochemical analysis, liver histopathology, and cell viability showed that NDD effectively relieved the liver injury. It reduced the accumulation of labile iron and alleviated lipid peroxidation by enhancing GPX4 activity. The mitochondrial morphology indicated that NDD exerted its hepatoprotective effect through an antiferroptotic activity. Metabolomic analysis showed that NDD treatment increased the levels of cysteine, decreased those of glutamate, and ameliorated the D-GalN/LPS-induced reduction in the levels of glutathione (GSH). The results for intracellular levels of reduced (GSH) and oxidized (GSSG) glutathione were consistent with those of metabolomic analysis.

Conclusion: Our findings indicate that NDD exerts hepatoprotective activity by evoking the reprogramming of GSH metabolism, and thereby, inhibiting ferroptosis.
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http://dx.doi.org/10.1016/j.jep.2021.114305DOI Listing
June 2021

The effect of cell isolation methods on the human transcriptome profiling and microbial transcripts of peripheral blood.

Mol Biol Rep 2021 Apr 30;48(4):3059-3068. Epub 2021 Apr 30.

BGI-Shenzhen, Shenzhen, 518083, China.

The expression of human and microbial genes serves as biomarkers for disease and health. Blood RNA is an important biological resource for precision medicine and translational medicine. However, few studies have assessed the human transcriptome profiles and microbial communities composition and diversity of peripheral blood from different cell isolation methods, which could affect the reproducibility of researches. We collected peripheral blood from three healthy donors and processed it immediately. We used RNA sequencing to investigate the effect of three leukocyte isolation methods including buffy coat (BC) extraction, red blood cell (RBC) lysis and peripheral blood mononuclear cell (PBMC) isolation with the comparison with whole blood (WB), through analyzing the sensitivity of gene detection, the whole transcriptome profiling and microbial composition and diversity. Our data showed that BC extraction with high globin mRNA mapping rate had similar transcriptome profiles with WB, while RBC lysis and PBMC isolation depleted RBCs effectively. With the efficient depletion of RBC and distinct compositions of leukocyte subsets, RNA-seq of RBC lysis and PBMC isolation uniquely detected genes from specific cell types, like granulocytes and NK cells. In addition, we observed that the microbial composition and diversity were more affected by individuals than isolation methods. Our results showed that blood cell isolations could largely influence the sensitivity of detection of human genes and transcriptome profile.
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http://dx.doi.org/10.1007/s11033-021-06382-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085658PMC
April 2021

The effect of pro/synbiotics on postoperative infections in colorectal cancer patients: A systematic review and meta-analysis.

Complement Ther Clin Pract 2021 May 1;43:101370. Epub 2021 Apr 1.

Department of Gastroenterology, The Second Clinical Medical College, Guangdong Medical University, Dongguan, Guangdong, 523808, China. Electronic address:

In 1954, the term "probiotics" was coined by Ferdinand Vergin in his article. Although there are many clinical reports on the use of pro/synbiotics and other microbial preparations to prevent postoperative infections and related complications in patients with Colorectal cancer (CRC), their effectiveness remains divided. Therefore, we collected relevant high-quality randomized controlled trial (RCT) studies and conducted systematic review and meta-analysis. We electronically searched online databases (the PubMed, EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Allied and Alternative Medieine (AMED), China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu) for literature published until December 2020. These reports were rigorously screened, and the data extracted, assessed for risk of bias (ROB), and subjected to meta-analysis and subgroup analysis. Postoperative infections were the main criteria for outcomes. Nineteen high-quality articles were included, involving 1975 patients. Compared with the control group, the pro/synbiotics group had reduced total postoperative infections ((odds ratio)OR = 0.28, 95% (confidence interval)CI: 0.20; 0.39, p < 0.0001), which included surgical site infections (SSI) (OR = 0.43, 95% CI: 0.31; 0.58, p < 0.0001) and non-surgical site infections (non-SSI) (OR = 0.28 95% CI: 0.20; 0.39, p < 0.0001).What is more, in aspects of inflammatory factors, intestinal dysbiosis, non-infectious complications, and systemic symptoms, the treatment group was better than the control group. However, there were no differences in perineal infections (OR = 0.45, 95% CI: 0.13; 1.50, p = 0.1933), celiac infections (OR = 0.54, 95% CI: 0.11; 2.66, p = 0.4471), or systemic inflammatory response syndrome (SIRS) incidence (OR = 0.63, 95% CI: 0.31; 1.30, p = 0.2139), etc. There were no differences in intervention (probiotics or synbiotics), strain type (multistrain or non-multistrain probiotics), and intervention time (administration preoperatively or pre-and-postoperatively). Pro/synbiotics can effectively prevent postoperative infections and related complications in patients with CRC. The strain type and intervention time did not affect the treatment effects.
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http://dx.doi.org/10.1016/j.ctcp.2021.101370DOI Listing
May 2021

Cloning and expression of gene in two varieties.

J Genet 2021 ;100

College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, People's Republic of China.

is an important regulator for flowering in plants and critical in controlling the morphogenesis of flower organs. The fulllength cDNAs of in conventional Lonicera macranthoides () and the mutant '' cultivar () were obtained using rapid amplification of cDNA ends and the expression vectors for were constructed to investigate the roles of in the cultivar. (GenBank: MK419948) and (GenBank: MK419948) were isolated from the conventional variety and '' cultivar respectively. is 1274 bp in length, whereas is 1264-bp long, and both include a 654 bp open reading frame, encoding 217 amino acids, which has a highly conserved MADS_MEF2_like domain and a moderately conserved K-box domain, belonging to the type II MADS-box family of genes. Quantitative real-time polymerase chain reaction indicated that the expression levels of these genes at different flowering stages were significantly different, and that the genes were also expressed in stems and leaves. is underexpressed at flowering period 5 that the key time node for corolla expansion and nonexpansion, while is overexpressed during this flowering period. was speculated to be a functional gene causing different phenotypes in the two varieties. The successfully constructed plant expression vector provides an experimental reference for further research on the function of this gene and the basis for the excellent phenotype of ''.
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January 2021

Epiregulin confers EGFR-TKI resistance via EGFR/ErbB2 heterodimer in non-small cell lung cancer.

Oncogene 2021 Apr 9;40(14):2596-2609. Epub 2021 Mar 9.

Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are effective against non-small cell lung cancer (NSCLC) with EGFR-activating mutations. The mechanisms underlying EGFR-TKI resistance are not fully understood. This study aimed to analyze the effects of seven EGFR ligands on EGFR-TKI sensitivity in NSCLC cells and patients. Cells with EGFR E746-A750del mutation were treated with recombinant EGFR ligands, and analyzed for cell viability, proliferation, and apoptosis. shRNA knockdown of endogenous Epiregulin (EREG) or overexpression of exogenous EREG and immunofluorescence experiments were carried out. Public gene expression datasets were used for tumor microenvironment and clinical assessment. Among the EGFR ligands, EREG significantly diminished cellular sensitivity to TKIs and was associated with decreased response to erlotinib in NSCLC patients. EREG induced AKT phosphorylation and attenuated TKI-induced cellular apoptosis in an ErbB2-dependent manner. EREG induced the formation of the EGFR/ErbB2 heterodimer regardless of gefitinib treatment. However, overexpression or knockdown of EREG in cancer cells had little impact on TKI sensitivity. Single-cell RNA sequencing data revealed that EREG was predominantly expressed in macrophages in the tumor microenvironment. In addition, EREG-enriched macrophage conditional medium induced EGFR-TKI resistance. These findings shed new light on the mechanism underlying EGFR-TKI resistance, and suggest macrophage-produced intratumoral EREG as a novel regulator and biomarker for EGFR-TKI therapy in NSCLC.
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http://dx.doi.org/10.1038/s41388-021-01734-4DOI Listing
April 2021

Impact of storage conditions on peripheral leukocytes transcriptome.

Mol Biol Rep 2021 Feb 9;48(2):1151-1159. Epub 2021 Feb 9.

BGI-Shenzhen, Shenzhen, 518083, China.

Leukocytes reflect the physiological and pathological states of each individual, and transcriptomic data of leukocytes have been used to reflect health conditions. Since the overall impact of ex vivo conditions on the leukocyte transcriptome before RNA stabilization remains unclear, we evaluated the influence of temporary storage conditions on the leukocyte transcriptome through RNA sequencing. We collected peripheral blood with EDTA tubes, which were processed immediately or stored either at 4 °C or room temperature (RT, 18-22 °C) for 2 h, 6 h and 24 h. Total cellular RNA was extracted from 42 leukocyte samples after red blood cells lysis for subsequent RNA sequencing. We applied weighted gene co-expression network analysis to construct co-expression networks of mRNA and lncRNA among the samples, and then performed gene ontology (GO) term enrichment to explore possible biological processes affected by storage conditions. Storage conditions change the gene expression of peripheral leukocytes. Comparing with fresh leukocytes, storage for 24 h at 4 °C and RT affected 1515 (1.51%) and 10,823 (10.82%) genes, respectively. Pathway enrichment analysis identified nucleosome assembly enriched in up-regulated genes at both conditions. When blood was stored at RT for 24 h, genes involved in apoptotic signaling pathway, negative regulation of cell cycle and lymphocyte activation were upregulated, while the relative proportion of neutrophils was significantly decreased. Temporary storage conditions profoundly affect the gene expression profiles of leukocytes and might further change cell viability and state. Storage of blood samples at 4 °C within 6 h largely maintains their original transcriptome.
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http://dx.doi.org/10.1007/s11033-021-06194-3DOI Listing
February 2021

A new species of (Anura, Rhacophoridae) from Guizhou, China.

Zool Res 2021 Mar;42(2):227-233

Key Laboratory of Ecology of Rare and Endangered Species and Environmental Protection (Guangxi Normal University), Ministry of Education, Guilin, Guangxi 541004, China.

We describe a new species of the genus , ., from Guizhou Province, China, based on morphological and molecular evidence. Phylogenetically, the new species is sister to , but is distinguishable from all known congeners by a combination of the following characters: small body size (snout-vent length 28.2‒32.2 mm in males; 38.6 mm in female); snout rounded, with no prominence on tip; single internal vocal sac; dorsal surface brown, rough, scattered with several small warts; chin clouded with blackish marking; pair of large symmetrical dark blotches on chest; vomerine teeth present; iris brown; tibiotarsal articulation reaching center of eye; nuptial pad slight; flank rough; mandibular symphysis weak; throat skin granular; and toes moderately webbed, formula I2‒2II1.5‒3III2‒3IV3‒2V. The genetic distances between the new species and were 2.9% and 5.4% for 16S rRNA and COI, respectively.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2020.311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995278PMC
March 2021

Inhibition of miR-494-3p alleviates oxidative stress-induced cell senescence and inflammation in the primary epithelial cells of COPD patients.

Int Immunopharmacol 2021 Mar 15;92:107044. Epub 2021 Jan 15.

Center of General Practice, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China; Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu 610072, China. Electronic address:

Background: Chronic obstructive pulmonary disease (COPD) is a disease associated with accelerated aging that threatens the lives of people worldwide and imposes heavy social and economic burdens. Cellular senescence is commonly observed in COPD and contributes to aging-related diseases.

Purpose: To identify the possible molecular pathways modulating cellular senescence in COPD.

Methods: MiR-494-3p expression levels in COPD tissues, small airway epithelial cells (SAECs) and BEAS-2B cells were detected by qRT-PCR. After transfection with miR-494-3p mimic or inhibitor in COPD SAECs, miR-494-3p modulation of senescence markers and senescence-associated secretory phenotype (SASP) proteins was detected. A luciferase assay was employed to verify the direct binding of SIRT3 and miR-494-3p. VX745 and c-myc siRNA were used to investigate the regulation of p38MAPK and c-myc by miR-494-3p.

Results: As a result of oxidative stress, MiR-494-3p was increased via the p38MAPK-c-myc signaling pathway in the lung tissues and cells of patients with COPD, and the increase in miR-494-3p was accompanied by increases in senescence markers (p27, p21 and p16) and SASP proteins (IL-1β, TNF-α, MMP2 and MMP9). MiR-494-3p was directly bound to SIRT3 in SAECs and was involved in cellular senescence. The upregulation of miR-494-3p decreased SIRT3 expression while increasing p27 expression in SAECs. Inhibition of miR-494-3p in SAECs from COPD patients reduced cell cycle arrest and the expression of SASP proteins (IL-1β, TNF-α, MMP2 and MMP9).

Conclusion: MiR-494-3p expression can be induced by oxidative stress via the p38MAPK-c-myc signaling pathway, and miR-494-3p can directly bind to SIRT3 to reduce its expression, leading to increased cellular senescence and thereby contributing to COPD progression.
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http://dx.doi.org/10.1016/j.intimp.2020.107044DOI Listing
March 2021

Generation of induced pluripotent stem cell GZLSL-i001-A derived from urine-derived cells of Hemophilia A patient with Inv22 mutation.

Stem Cell Res 2020 12 19;49:102053. Epub 2020 Oct 19.

Key Lab for Major Obstetric Diseases of Guangdong Province, Experimental Department of Institute of Gynecology and Obstetrics, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong Province, China. Electronic address:

Hemophilia A (HA), is a X-linked recessive congenital bleeding disorder, caused by deficiency of the coagulation factorVIII (FVIII) which is encoded by coagulation factor 8 (F8). HA affects 1 of every 5,000 males worldwide. The intron 22 inversion (Inv22) mutation of F8 causes about 45% of severeHA cases.Here, we generated induced pluripotent stem cells (iPSCs) from a HA patient with Inv22 mutation by electroporation of urine-derived cells (UCs) with episomal plasmids under feeder-free, virus-free, serum-free condition and without oncogene c-MYC. This iPSCs line could facilitate future applications of human iPSCs by provide a valuable cell model.
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http://dx.doi.org/10.1016/j.scr.2020.102053DOI Listing
December 2020

Characterization of Metabolic Patterns in Mouse Oocytes during Meiotic Maturation.

Mol Cell 2020 11 16;80(3):525-540.e9. Epub 2020 Oct 16.

State Key Laboratory of Reproductive Medicine, Suzhou Municipal Hospital, Nanjing Medical University, Nanjing 211166, China; Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address:

Well-balanced and timed metabolism is essential for making a high-quality egg. However, the metabolic framework that supports oocyte development remains poorly understood. Here, we obtained the temporal metabolome profiles of mouse oocytes during in vivo maturation by isolating large number of cells at key stages. In parallel, quantitative proteomic analyses were conducted to bolster the metabolomic data, synergistically depicting the global metabolic patterns in oocytes. In particular, we discovered the metabolic features during meiotic maturation, such as the fall in polyunsaturated fatty acids (PUFAs) level and the active serine-glycine-one-carbon (SGOC) pathway. Using functional approaches, we further identified the key targets mediating the action of PUFA arachidonic acid (ARA) on meiotic maturation and demonstrated the control of epigenetic marks in maturing oocytes by SGOC network. Our data serve as a broad resource on the dynamics occurring in metabolome and proteome during oocyte maturation.
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http://dx.doi.org/10.1016/j.molcel.2020.09.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034554PMC
November 2020

Propofol‑induced miR‑125a‑5p inhibits the proliferation and metastasis of ovarian cancer by suppressing LIN28B.

Mol Med Rep 2020 Aug 11;22(2):1507-1517. Epub 2020 Jun 11.

Department of Obstetrics, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.

Propofol, a commonly used intravenous anesthetic agent during surgery, has relatively widespread pharmacological actions. Previous studies have reported that propofol may act as an antitumor drug in several cancer types, such as pancreatic cancer, lung cancer and gastric cancer. However, the underlying mechanism in ovarian cancer remain unknown. Therefore, the present study investigated the pharmacological effect of propofol on microRNAs (miRNAs) in ovarian cancer treatment. Propofol (1, 5 or 10 µg/ml) was used to treat A2780 and SKOV3 ovarian cancer cells for 1, 2, 3, 4 or 5 days. The MTT assay was used to detect cell viability, while wound healing and Transwell assays were utilized to assess the invasive and migratory abilities. The bioinformatics prediction approach identified differentially expressed miRNAs (miRs) that were used in Gene Ontology, Gene Set Enrichment Analysis and Kyoto Encyclopedia of Genes and Genomes analyses. The expression levels of miR‑125a‑5p and lin‑28 homolog B (LIN28B) were evaluated by reverse transcription‑quantitative PCR (RT‑qPCR). A luciferase assay was performed to identify the relationship between miR‑125a‑5p and LIN28B. Western blotting was conducted to measure the protein expression of LIN28B. It was demonstrated that propofol significantly upregulated miR‑125a‑5p to exert its antitumor activity. RT‑qPCR results suggested that propofol could upregulate miR‑125a‑5p and LIN28B expression levels in ovarian cancer cell lines. Western blot analysis also indicated that propofol could enhance the expression of LIN28B in ovarian cancer cell lines. The luciferase assay identified that miR‑125a‑5p could directly inhibit the expression of LIN28B to suppress proliferation and metastasis in ovarian cancer. In conclusion, these results suggested that propofol inhibited ovarian cancer proliferation and metastasis by enhancing miR‑125a‑5p, which targets LIN28B.
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http://dx.doi.org/10.3892/mmr.2020.11223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346589PMC
August 2020

Transcription levels and prognostic significance of the NFI family members in human cancers.

PeerJ 2020 18;8:e8816. Epub 2020 Mar 18.

The First Oncology Department, Shengjing Hospital affiliated with China Medical University, Shenyang, China.

Background: The nuclear factor I (NFI) is a family of transcription factors consisting of four distinct but closely related genes, NFIA, NFIB, NFIC and NFIX, which are important in the development of various tissues and organs in mammals. Recent study results have shown that NFI family may play a critical role in the progression of various human tumors and have been identified as key tumor suppressors and oncogenes for many cancers. However, the expression levels and distinctive prognostic values of the NFI family remain poorly explored in most cancers.

Materials And Methods: In the present study, the differences in mRNA expression of the NFI family in various cancers were investigated using the Oncomine and TCGA databases, and the mRNA expression, genetic alteration and DNA methylation of the NFI family members in various cancers were examined using cBioPortal for Cancer Genomics. In addition, the prognostic significance of the NFI family was assessed in multiple cancers using the Kaplan-Meier plotter (KM plotter) and SurvExpress databases.

Results: The mRNA expression levels in the NFI family were significantly downregulated in most cancers compared with normal tissues and DNA hypermethylation might downregulate the NFI family expression. Although NFIX expression was not downregulated in kidney, colorectal and prostate cancers. Furthermore, NFIB expression was upregulated in gastric cancer. Further survival analyses based on the KM plotter and SurvExpress databases showed dysregulations of the NFI genes were significantly correlated with survival outcomes in breast, lung, and head and neck cancers. Decreased expression levels of NFIA, NFIB and NFIC were associated with poor overall survival (OS) in head and neck cancer. Low mRNA expression of NFIA and NFIB was significantly associated with OS and first progression in lung adenocarcinoma, but not in lung squamous cell carcinoma. In addition, potential correlations between NFI family members and survival outcomes were also observed in liver, esophageal, kidney and cervical cancer.

Conclusion: The results from the present study indicated certain members of the NFI family could be promising therapeutic targets and novel prognostic biomarkers for human cancers.
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http://dx.doi.org/10.7717/peerj.8816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085295PMC
March 2020

[Incidence and mortality risk factors of acute kidney injury in critical ill pregnancies: a single center retrospective analysis].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2019 Dec;31(12):1506-1511

Department of ICU, Shandong University Affiliated Provincial Hospital, Jinan 250021, Shandong, China.

Objective: To evaluate the incidence and mortality risk factors of pregnancy-related acute kidney injury (PR-AKI) in intensive care unit (ICU).

Methods: A retrospective analysis was conducted. Critically ill pregnancies admitted to ICU of Shandong University Affiliated Provincial Hospital from January 1st, 2012 to December 31st, 2016 were enrolled. Based on the Kidney Disease: Improving Global Outcomes (KDIGO)-acute kidney injury (AKI) criteria, patients were divided into two groups: PR-AKI group and non-PR-AKI group. Clinical characteristics and laboratory data of two groups were compared. Risk factors of incidence and mortality of PR-AKI patients were analyzed, and the receiver operating characteristic (ROC) curve was drawn to evaluate the value of these risk factors in predicting mortality of PR-AKI patients in ICU.

Results: (1) A total of 219 pregnancies in ICU were included in the analysis, 85 cases (38.8%) were diagnosed with PR-AKI, with 29.4% in AKI stage 1, 27.1% in AKI stage 2 and 43.5% in AKI stage 3. (2) Nineteen of 219 critically ill pregnancies died in ICU, the total ICU mortality was 8.7%. The mortality of PR-AKI group was higher than non-PR-AKI group (16.5% vs. 3.7%, P = 0.003). The mortality was worsened with increasing severity of AKI (4.0% for AKI stage 1, 4.3% for AKI stage 2, 32.4% for AKI stage 3). (3) Acute fatty liver of pregnancy (AFLP) and lactate (Lac) were the independent risk factors for PR-AKI [AFLP: odds ratio (OR) = 6.081, 95% confidence interval (95%CI) was 1.587-23.308, P = 0.008; Lac: OR = 1.460, 95%CI was 1.078-1.977, P = 0.014]. (4) Age, Lac, acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) were the independent risk factors associated with the mortality of PR-AKI patients in ICU (age: OR = 1.130, 95%CI was 1.022-1.249, P = 0.017; Lac: OR = 1.198, 95%CI was 1.009-2.421, P = 0.039; APACHE II: OR = 1.211, 95%CI was 1.102-1.330, P < 0.001; SOFA: OR = 1.411, 95%CI was 1.193-1.669, P < 0.001). (5) ROC curve analysis showed that age, Lac, APACHE II score and SOFA score all had good predictive values for in-hospital mortality among PR-AKI patients in ICU, the cut-off value was 29 years old, 3.8 mmol/L, 16 and 8, respectively, and the AUC was 0.751, 0.757, 0.892 and 0.919, respectively (all P < 0.01).

Conclusions: The incidence and mortality of PR-AKI of critically ill pregnancies in ICU are high. Increased age, Lac, APACHE II score and SOFA score are independent risk factors associated with the mortality of PR-AKI patients in ICU, and have good predictive values for prognosis.
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http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2019.12.014DOI Listing
December 2019

Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) in non-small cell lung cancer.

Life Sci 2020 Aug 15;254:117325. Epub 2020 Jan 15.

Department of Cardiothoracic Surgery, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning 437000, PR China. Electronic address:

Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is a transcription factor that can regulate downstream target gene expression. Kelch-like ECH-associated protein 1 (Keap1) negatively regulates Nrf2 activation and translocation to target its 26S proteasomal degradation. It has been widely reported that the Keap1/Nrf2 pathway is associated with tumorigenesis, chemotherapy resistance and progression and development of non-small cell lung cancer (NSCLC). High expression of Nrf2 and low abundance of Keap1 contribute to the abnormalities and unrealistic treatment prognosis of NSCLC. Therefore, elucidating the role and potential mechanism of Nrf2 in NSCLC is essential for understanding tumorigenesis and for the development of strategies for effective clinical management. Here, we summarize current knowledge about the molecular structure and biological function of Nrf2, and we discuss the roles of Nrf2 in tumorigenesis, which will further provide a possible therapeutic strategy for NSCLC.
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http://dx.doi.org/10.1016/j.lfs.2020.117325DOI Listing
August 2020

Improving UV Resistance of Aramid Fibers by Simultaneously Synthesizing TiO on Their Surfaces and in the Interfaces Between Fibrils/Microfibrils Using Supercritical Carbon Dioxide.

Polymers (Basel) 2020 Jan 7;12(1). Epub 2020 Jan 7.

School of Materials Engineering, Shanghai University of Engineering Science, Shanghai 201600, China.

Aramid fibers with low density and high strength, modulus, and thermal resistance are widely used in applications such as bulletproof vests and cables. However, owing to their chemical structure, they are sensitive to ultraviolet light, which degrades the fibers' useful mechanical properties. In this study, titanium dioxide (TiO) nanoparticles were synthesized both on the aramid III fiber surface and in the interfacial space between the fibrils/microfibrils in supercritical carbon dioxide (scCO) to improve the UV resistance of aramid fibers. The effects of scCO treatment pressure on the TiO structure, morphology, surface composition, thermal stability, photostability, and mechanical properties were investigated using Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis, ultraviolet-visible spectroscopy, and single-fiber test. The results show that amorphous TiO formed on the fiber surface and the interface between fibrils/microfibrils, and decreased the photodegradation rate of the aramid III fiber. Moreover, this modification can also improve the tensile strength via treatment at low temperature and without the use of a solvent. The simple synthesis process in scCO, which is scalable, is used for mild modifications with a green solvent, providing a promising technique for synthesizing metal dioxide on polymers.
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http://dx.doi.org/10.3390/polym12010147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022332PMC
January 2020

In a Rat Model of Acute Liver Failure, Icaritin Improved the Therapeutic Effect of Mesenchymal Stem Cells by Activation of the Hepatocyte Growth Factor/c-Met Pathway.

Evid Based Complement Alternat Med 2019 7;2019:4253846. Epub 2019 Nov 7.

The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, China.

Acute liver failure (ALF) is a serious life-threatening condition. Mesenchymal stem cells (MSCs) may be an effective treatment for this condition and a good alternative to liver transplantation. Icaritin (ICT) is an active ingredient of the genus , a traditional Chinese medicine, with the potential to enhance the proliferation of MSCs. The purpose of this study was to explore whether ICT increased the therapeutic effects of MSCs and explore its underlying mechanisms. For experiments, a rat ALF model was established by intraperitoneal injection of D(+)-galactosamine/ lipopolysaccharide. MSCs cocultured with ICT were used to treat ALF rats and the protective effects assessed as survival rate, levels of serum AST and ALT, and histological changes in liver tissue. For experiments, MSCs were treated in serum-free culture for 72 h to simulate the disruption of intrahepatic microcirculation. MSCs apoptosis was examined to determine whether ICT rescued impaired MSCs. The role of the hepatocyte growth factor (HGF)/c-Met pathway in MSCs was assessed by constructing genetically modified MSCs overexpressing c-Met and by using the c-Met receptor inhibitor (crizotinib). The results showed that MSCs increased the survival rate of ALF rats and reduced liver damage. MSCs cocultured with ICT exerted a greater therapeutic effect than MSCs alone. Further, the HGF/c-Met pathway played a key role in the antiapoptotic activity of MSCs, which was associated with the optimized efficacy of ICT. In conclusion, this study demonstrated that ICT enhances the therapeutic effect of MSCs in a model of ALF, improving the antiapoptotic potential of MSCs by upregulation of the HGF/c-Met pathway. The combination of stem cell therapy with traditional herbal extracts may improve MSC-based clinical applications.
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http://dx.doi.org/10.1155/2019/4253846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935441PMC
November 2019

CXCL9 regulates acetaminophen-induced liver injury via CXCR3.

Exp Ther Med 2019 Dec 23;18(6):4845-4851. Epub 2019 Oct 23.

Department of General Practice, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.

Drug-induced liver injury has become a serious public health problem. Although the mechanism of acetaminophen (APAP)-induced liver injury has been studied for decades it has not been fully elucidated. In-depth study into the mechanisms underlying APAP-induced liver injury may provide useful information for more effective prevention and treatment. In the present study, the role of C-X-C motif chemokine ligand-9 (CXCL9) in APAP-induced liver injury was investigated thus providing a novel direction for the prevention and treatment of drug hepatitis. A total of 20 fasting male patients ingested APAP tablets at Nanjing First Hospital. In addition, wild type (WT) mice were treated with 250 mg/kg APAP or isodose PBS for 1, 3, 6 and 12 h, respectively. Results from reverse-transcription-quantitative polymerase chain reaction analyses demonstrated that CXCL9 mRNA levels were increased in the blood of patients who took APAP in a fasting state and in the livers of APAP-treated WT mice, compared with their respective controls. Hepatocyte apoptosis in the liver tissue of APAP-treated mice decreased following administration of a CXCL9 neutralizing antibody. Caspase-3, caspase-8 and phosphorylated-AKT (S437) were activated in primary hepatocytes isolated from WT mice following CXCL9 treatment. However, no significant differences in expression of caspase-3, caspase-8 and p-AKT (S437) were detected in hepatocytes isolated from C-X-C motif chemokine receptor 3 (CXCR3) mice following CXCL9 treatment. After CXCL9 administration, WT mice exhibited higher serum levels of aspartate transaminase and increased caspase-3 and caspase-8 activity in liver tissue compared with controls. The same trends were not observed in CXCR3 mice. In conclusion, CXCL9 regulated APAP-induced liver injury through stimulation of hepatocyte apoptosis via binding to CXCR3. These findings provide a novel prevention and treatment strategy for DILI.
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http://dx.doi.org/10.3892/etm.2019.8122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861945PMC
December 2019

A meta-analysis on relationship between paraoxonase 1 polymorphisms and atherosclerotic cardiovascular diseases.

Life Sci 2019 Sep 11;232:116646. Epub 2019 Jul 11.

Center of General Practice, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China. Electronic address:

Background: Some previous studies already explored associations between paraoxonase 1 (PON1) polymorphisms and atherosclerotic cardiovascular diseases (ASCVD), with conflicting findings. Here, we aimed to better analyze the relationship between PON1 polymorphisms and ASCVD in a larger combined population by performing a meta-analysis.

Methods: We searched Pubmed, Embase and Web of Science for related articles. We calculated odds ratio (OR) and 95% confidence interval (CI) to estimate whether there are genetic associations between PON1 polymorphisms and ASCVD.

Results: One hundred and nine studies were included for this meta-analysis. The PON1 rs854560 (17,220 cases and 18,570 controls, recessive comparison: OR = 0.83, 95%CI 0.72-0.96) and rs662 (30,717 cases and 54,894 controls, dominant comparison: OR = 0.82, 95% CI 0.77-0.89; recessive comparison: OR = 1.17, 95% CI 1.07-1.28; allele comparison: OR = 0.85, 95% CI 0.81-0.90) polymorphisms were both found to be significantly associated with susceptibility to ASCVD in general population. Subgroup analyses by ethnicity revealed similar significant findings for rs854560 polymorphism only in East Asians, while similar positive findings for rs662 polymorphism were observed in Caucasians, East Asians and South Asians. Subgroup analyses by type of disease indicated that the significant findings for rs854560 polymorphism were mainly driven by the ischemic stroke (IS) subgroup, whereas the positive results for rs662 polymorphism were mainly driven by the coronary artery disease (CAD) subgroup.

Conclusions: In summary, this meta-analysis proved that PON1 rs854560 polymorphism could be used to identify individual with elevated susceptibility to IS, whereas rs662 polymorphism could be used to identify individual with elevated susceptibility to CAD.
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http://dx.doi.org/10.1016/j.lfs.2019.116646DOI Listing
September 2019

ceRNA network analysis reveals prognostic markers for glioblastoma.

Oncol Lett 2019 Jun 18;17(6):5545-5557. Epub 2019 Apr 18.

Department of Oncology, Shengjing Hospital, China Medical University, Shenyang, Liaoning 110004, P.R. China.

Glioblastoma (GBM) is a common aggressive cancer that originates in the brain, which has a poor prognosis. It is therefore crucial to understand its underlying genetic mechanisms in order to develop novel therapies. The present study aimed to identify some prognostic markers and candidate therapeutic targets for GBM. To do so, RNA expression levels in tumor and normal tissues were compared by microarray analysis. The differential expression of RNAs in normal and cancer tissues was analyzed, and a competing endogenous RNA (ceRNA) network was constructed for pathway analysis. The results revealed that RNA expression patterns were considerably different between normal and tumor samples. A ceRNA network was therefore constructed with the differentially expressed RNAs. ETS variant 5 (), myocyte enhancer factor 2C and ETS transcription factor () were considerably enriched in the significant pathway of 'transcriptional misregulation in cancer'. In addition, prognostic analysis demonstrated that and expression levels were associated with the survival time of patients with GBM. These results suggested that and may be prognostic markers for GBM, and that their microRNAs may be candidate therapeutic targets.
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http://dx.doi.org/10.3892/ol.2019.10275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507312PMC
June 2019

A novel role for NFIA in restoring radiosensitivity in radioresistant NSCLC cells by downregulating the AKT and ERK pathways.

Biochem Biophys Res Commun 2019 08 6;515(4):558-564. Epub 2019 Jun 6.

The First Oncology Department, Shengjing Hospital Affiliated with China Medical University, Shenyang, 110004, China. Electronic address:

Radioresistance remains the most challenging issue leading to radiotherapy failure in the treatment of non-small cell lung cancer (NSCLC). The nuclear factor IA (NFIA) is associated with tumor response to treatments in many cancers, but its role in NSCLC radioresistance remains unclear. Here, we established two radioresistant NSCLC cell lines, H226R and H460R, by dose-gradient irradiation to investigate the function of NFIA in NSCLC radioresistance. The results showed a dramatically reduced expression of NFIA in radioresistant cells accompanied with elevated phosphorylation of AKT and ERK, when compared with their parental cells. Overexpression of NFIA restored the sensitivity of radioresistant cells to radiation through increased ionizing radiation (IR)-induced apoptosis and DNA damage by downregulating p-AKT and p-ERK, whereas knockdown of NFIA promoted radioresistance of the parental cells. Our findings suggested that NFIA enhanced cell radiosensitivity by downregulating p-AKT and p-ERK in NSCLC. Our study fills a gap in the field of NFIA and radioresistance, and establishes a mechanistic foundation to improve radiotherapy efficiency in NSCLC patients.
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http://dx.doi.org/10.1016/j.bbrc.2019.06.011DOI Listing
August 2019

Robust estimation of sediment sound speed from the group speed of the critical mode.

J Acoust Soc Am 2019 Mar;145(3):EL243

School of Earth and Ocean Sciences, University of Victoria, Victoria, British Columbia V8P 5C2,

In the ocean waveguide, the sediment sound speed has a simple relationship with the group speed of the highest order mode that propagates close to the critical angle. The paper shows that robust estimates of the sound speed are obtained from estimates of the "critical" mode group speed determined from analysis of the energy distribution of the time-warped spectrum of a broadband signal. The method is applied to experimental data collected in the Yellow Sea of China. Estimated sound speeds agreed closely with expected values for clayey slit (1531 m/s) and sandy silt (1593 m/s) sediment at the sites.
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http://dx.doi.org/10.1121/1.5094667DOI Listing
March 2019

SIRT6 participates in the quality control of aged oocytes via modulating telomere function.

Aging (Albany NY) 2019 03;11(7):1965-1976

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.

It has been well recognized that oocyte quality declines in aging animals. However, to date, the underlying mechanism remains to be explored. In the present study, we report that oocytes and embryos from aged mice (42-45 weeks old) display the reduced expression of SIRT6 protein, accompanying with telomere shortening and DNA lesions. Moreover, we demonstrate that specific depletion of SIRT6 in oocytes induces dysfunctional telomeres and apoptosis of the resultant early embryos, leading to the developmental delay and cytoplasmic fragmentation. Importantly, we further find that overexpression of SIRT6 in aged oocytes promotes the telomere elongation in 2-cell embryos and lowers the incidence of apoptotic blastomeres. In summary, our data indicate a role for SIRT6 in modulating telomere function during oocyte maturation and embryonic development, and discover that SIRT6 reduction is an important point connecting maternal aging and quality control of oocyte/embryos.
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http://dx.doi.org/10.18632/aging.101885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503879PMC
March 2019

NMNAT2-mediated NAD generation is essential for quality control of aged oocytes.

Aging Cell 2019 06 25;18(3):e12955. Epub 2019 Mar 25.

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.

Advanced maternal age has been reported to impair oocyte quality; however, the underlying mechanisms remain to be explored. In the present study, we identified the lowered NAD content and decreased expression of NMNAT2 protein in oocytes from old mice. Specific depletion of NMNAT2 in mouse oocytes disturbs the meiotic apparatus assembly and metabolic activity. Of note, nicotinic acid supplementation during in vitro culture or forced expression of NMNAT2 in aged oocytes was capable of reducing the reactive oxygen species (ROS) production and incidence of spindle/chromosome defects. Moreover, we revealed that activation or overexpression of SIRT1 not only partly prevents the deficient phenotypes of aged oocytes but also ameliorates the meiotic anomalies and oxidative stress in NMNAT2-depleted oocytes. To sum up, our data indicate a role for NMNAT2 in controlling redox homeostasis during oocyte maturation and uncover that NMNAT2- NAD -SIRT1 is an important pathway mediating the effects of maternal age on oocyte developmental competence.
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http://dx.doi.org/10.1111/acel.12955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516161PMC
June 2019

Correlations between methylenetetrahydrofolate reductase gene polymorphisms and venous thromboembolism: A meta-analysis of 99 genetic association studies.

Eur J Prev Cardiol 2019 01 22;26(2):120-134. Epub 2018 Nov 22.

Center of General Practice, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, China.

We performed this meta-analysis to better assess the relationship between methylenetetrahydrofolate reductase gene ( MTHFR) polymorphisms and the risk of venous thromboembolism. Eligible studies were searched in PubMed, Medline, Embase, and Web of Science. Odds ratios with 95% confidence intervals were used to assess associations of MTHFR polymorphisms with venous thromboembolism. A total of 99 genetic association studies were enrolled for analyses. Although no positive results were detected in overall analyses for the rs1801131 polymorphism. Further subgroup analyses according to ethnicity of participants and type of disease revealed that the rs1801131 polymorphism was significantly correlated with the risk of pulmonary embolism. For the rs1801133 polymorphism, significant association with the risk of venous thromboembolism was found in the dominant, recessive, and allele models. Further subgroup analyses according to ethnicity of participants revealed that the rs1801133 polymorphism was significantly associated with the risk of venous thromboembolism in Caucasians, East Asians, and West Asians. When we stratified available data according to type of disease, we found that the rs1801133 polymorphism was also significantly correlated with the risk of deep vein thrombosis and pulmonary embolism. In conclusion, our findings indicate that the MTHFR rs1801133 polymorphism may serve as a potential biological marker for venous thromboembolism in Caucasians, East Asians, and West Asians. Moreover, the MTHFR rs1801133 polymorphism may be implicated in the development of deep vein thrombosis and pulmonary embolism, while the MTHFR rs1801131 polymorphism may contribute to the development of pulmonary embolism.
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http://dx.doi.org/10.1177/2047487318799467DOI Listing
January 2019

From Levinthal's Paradox to the Effects of Cell Environmental Perturbation on Protein Folding.

Curr Med Chem 2019 ;26(42):7537-7554

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan Scientific Research Center, Guangdong Medical University, Dongguan, Guangdong 523808, China.

Background: The rapidly increasing number of known protein sequences calls for more efficient methods to predict the Three-Dimensional (3D) structures of proteins, thus providing basic knowledge for rational drug design. Understanding the folding mechanism of proteins is valuable for predicting their 3D structures and for designing proteins with new functions and medicinal applications. Levinthal's paradox is that although the astronomical number of conformations possible even for proteins as small as 100 residues cannot be fully sampled, proteins in nature normally fold into the native state within timescales ranging from microseconds to hours. These conflicting results reveal that there are factors in organisms that can assist in protein folding.

Methods: In this paper, we selected a crowded cell-like environment and temperature, and the top three Posttranslational Modifications (PTMs) as examples to show that Levinthal's paradox does not reflect the folding mechanism of proteins. We then revealed the effects of these factors on protein folding.

Results: The results summarized in this review indicate that a crowded cell-like environment, temperature, and the top three PTMs reshape the Free Energy Landscapes (FELs) of proteins, thereby regulating the folding process. The balance between entropy and enthalpy is the key to understanding the effect of the crowded cell-like environment and PTMs on protein folding. In addition, the stability/flexibility of proteins is regulated by temperature.

Conclusion: This paper concludes that the cellular environment could directly intervene in protein folding. The long-term interactions of the cellular environment and sequence evolution may enable proteins to fold efficiently. Therefore, to correctly understand the folding mechanism of proteins, the effect of the cellular environment on protein folding should be considered.
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http://dx.doi.org/10.2174/0929867325666181017160857DOI Listing
January 2020

Subgroup analysis reveals molecular heterogeneity and provides potential precise treatment for pancreatic cancers.

Onco Targets Ther 2018 12;11:5811-5819. Epub 2018 Sep 12.

Department of Oncology, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China,

Background: The relationship between molecular heterogeneity and clinical features of pancreatic cancer remains unclear. In this study, pancreatic cancer was divided into different subgroups to explore its specific molecular characteristics and potential therapeutic targets.

Patients And Methods: Expression profiling data were downloaded from The Cancer Genome Atlas database and standardized. Bioinformatics techniques such as unsupervised hierarchical clustering was used to explore the optimal molecular subgroups in pancreatic cancer. Clinical pathological features and pathways in each subgroup were also analyzed to find out the potential clinical applications and initial promotive mechanisms of pancreatic cancer.

Results: Pancreatic cancer was divided into three subgroups based on different gene expression features. Patients included in each subgroup had specific biological features and responded significantly different to chemotherapy.

Conclusion: Three distinct subgroups of pancreatic cancer were identified, which means that patients in each subgroup might benefit from targeted individual management.
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http://dx.doi.org/10.2147/OTT.S163139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140745PMC
September 2018

Structural Prediction of the Dimeric Form of the Mammalian Translocator Membrane Protein TSPO: A Key Target for Brain Diagnostics.

Int J Mol Sci 2018 Aug 31;19(9). Epub 2018 Aug 31.

Institute for Advanced Simulations (IAS)-5/Institute for Neuroscience and Medicine (INM)-9, Forschungszentrum Jülich, 52428 Jülich, Germany.

Positron emission tomography (PET) radioligands targeting the human translocator membrane protein (TSPO) are broadly used for the investigations of neuroinflammatory conditions associated with neurological disorders. Structural information on the mammalian protein homodimers-the suggested functional state of the protein-is limited to a solid-state nuclear magnetic resonance (NMR) study and to a model based on the previously-deposited solution NMR structure of the monomeric mouse protein. Computational studies performed here suggest that the NMR-solved structure in the presence of detergents is not prone to dimer formation and is furthermore unstable in its native membrane environment. We, therefore, propose a new model of the functionally-relevant dimeric form of the mouse protein, based on a prokaryotic homologue. The model, fully consistent with solid-state NMR data, is very different from the previous predictions. Hence, it provides, for the first time, structural insights into this pharmaceutically-important target which are fully consistent with experimental data.
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http://dx.doi.org/10.3390/ijms19092588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165245PMC
August 2018

Aggregation of lipid rafts activates c-met and c-Src in non-small cell lung cancer cells.

BMC Cancer 2018 May 30;18(1):611. Epub 2018 May 30.

The First Oncology Department, Shengjing Hospital affiliated with China Medical University, Shenyang, 110004, China.

Background: Activation of c-Met, a receptor tyrosine kinase, induces radiation therapy resistance in non-small cell lung cancer (NSCLC). The activated residual of c-Met is located in lipid rafts (Duhon et al. Mol Carcinog 49:739-49, 2010). Therefore, we hypothesized that disturbing the integrity of lipid rafts would restrain the activation of the c-Met protein and reverse radiation resistance in NSCLC. In this study, a series of experiments was performed to test this hypothesis.

Methods: NSCLC A549 and H1993 cells were incubated with methyl-β-cyclodextrin (MβCD), a lipid raft inhibitor, at different concentrations for 1 h before the cells were X-ray irradiated. The following methods were used: clonogenic (colony-forming) survival assays, flow cytometry (for cell cycle and apoptosis analyses), immunofluorescence microscopy (to show the distribution of proteins in lipid rafts), Western blotting, and biochemical lipid raft isolation (purifying lipid rafts to show the distribution of proteins in lipid rafts).

Results: Our results showed that X-ray irradiation induced the aggregation of lipid rafts in A549 cells, activated c-Met and c-Src, and induced c-Met and c-Src clustering to lipid rafts. More importantly, MβCD suppressed the proliferation of A549 and H1993 cells, and the combination of MβCD and radiation resulted in additive increases in A549 and H1993 cell apoptosis. Destroying the integrity of lipid rafts inhibited the aggregation of c-Met and c-Src to lipid rafts and reduced the expression of phosphorylated c-Met and phosphorylated c-Src in lipid rafts.

Conclusions: X-ray irradiation induced the aggregation of lipid rafts and the clustering of c-Met and c-Src to lipid rafts through both lipid raft-dependent and lipid raft-independent mechanisms. The lipid raft-dependent activation of c-Met and its downstream pathways played an important role in the development of radiation resistance in NSCLC cells mediated by c-Met. Further studies are still required to explore the molecular mechanisms of the activation of c-Met and c-Src in lipid rafts induced by radiation.
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http://dx.doi.org/10.1186/s12885-018-4501-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5977465PMC
May 2018

SIRT4 is essential for metabolic control and meiotic structure during mouse oocyte maturation.

Aging Cell 2018 08 29;17(4):e12789. Epub 2018 May 29.

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.

SIRT4 modulates energy homeostasis in multiple cell types and tissues. However, its role in meiotic oocytes remains unknown. Here, we report that mouse oocytes overexpressing SIRT4 are unable to completely progress through meiosis, showing the inadequate mitochondrial redistribution, lowered ATP content, elevated reactive oxygen species (ROS) level, with the severely disrupted spindle/chromosome organization. Moreover, we find that phosphorylation of Ser293-PDHE1α mediates the effects of SIRT4 overexpression on metabolic activity and meiotic events in oocytes by performing functional rescue experiments. By chance, we discover the SIRT4 upregulation in oocytes from aged mice; and importantly, the maternal age-associated deficient phenotypes in oocytes can be partly rescued through the knockdown of SIRT4. These findings reveal the critical role for SIRT4 in the control of energy metabolism and meiotic apparatus during oocyte maturation and indicate that SIRT4 is an essential factor determining oocyte quality.
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http://dx.doi.org/10.1111/acel.12789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052465PMC
August 2018
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