Publications by authors named "Ye Zhao"

465 Publications

Dietary isoleucine improved flesh quality, muscle antioxidant capacity, and muscle growth associated with AKT/TOR/S6K1 and AKT/FOXO3a signaling in hybrid bagrid catfish (Pelteobagrus vachelli♀ × Leiocassis longirostris♂).

J Anim Sci Biotechnol 2021 Apr 19;12(1):53. Epub 2021 Apr 19.

College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, 611130, China.

Background: Muscle is the complex and heterogeneous tissue, which comprises the primary edible part of the trunk of fish and mammals. Previous studies have shown that dietary isoleucine (Ile) exerts beneficial effects on growth in aquatic animals. However, there were limited studies regarding the benefits of Ile on fish muscle and their effects on flesh quality and muscle growth. Thus, this study was conducted to explore whether dietary Ile had affected flesh quality and muscle growth in hybrid bagrid catfish (Pelteobagrus vachelli♀ × Leiocassis longirostris♂).

Methods: A total of 630 hybrid fish, with an initial average body weight of 33.11 ± 0.09 g, were randomly allotted into seven experimental groups with three replicates each, and respectively fed seven diets with 5.0, 7.5, 10.0, 12.5, 15.0, 17.5, and 20.0 g Ile/kg diets for 8 weeks.

Results: In the present study, we demonstrated that Ile significantly: (1) increased muscle protein and lipid contents and the frequency distribution of myofibers with ≤ 20 μm and ≥ 50 μm of diameter; (2) improved pH value, shear force, cathepsin B and L activities, hydroxyproline content, resilience, cohesiveness, and decreased cooking loss, lactate content, hardness, springiness, gumminess, and chewiness; (3) decreased reactive oxygen species (ROS), malondialdehyde (MDA), and protein carbonyl (PC) contents, GCLC and Keap1 mRNA levels, and up-regulated CuZnSOD, CAT, GPX1a, GST, and Nrf2 mRNA levels; (4) up-regulated the insulin-like growth factor 1, 2 (IGF-1, IGF-2), insulin-like growth factor 1 receptor (IGF-1R), proliferating cell nuclear antigen (PCNA), Myf5, Myod, Myog, Mrf4, and MyHC mRNA levels, and decreased MSTN mRNA level; (5) increased muscle protein deposition by activating AKT-TOR-S6K1 and AKT-FOXO3a signaling pathways.

Conclusion: These results revealed that dietary Ile improved flesh quality, which might be due to increasing nutritional content, physicochemical, texture parameters, and antioxidant ability; promoting muscle growth by affecting myocytes hyperplasia and hypertrophy, and muscle protein deposition associated with protein synthesis and degradation signaling pathways. Finally, the quadratic regression analysis of chewiness, ROS, and protein contents against dietary Ile levels suggested that the optimal dietary Ile levels for hybrid bagrid catfish was estimated to be 14.19, 12.36, and 12.78 g/kg diet, corresponding to 36.59, 31.87, and 32.96 g/kg dietary protein, respectively.
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http://dx.doi.org/10.1186/s40104-021-00572-4DOI Listing
April 2021

Abnormalities of the PRMT1-ADMA-DDAH1 metabolism axis and probucol treatment in diabetic patients and diabetic rats.

Ann Palliat Med 2021 Mar;10(3):3343-3353

Department of Endocrinology and Metabolism, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China.

Background: Symmetrical dimethylarginine (ADMA) endogenously inhibits nitric oxide synthase (NOS) and strongly indicates oxidant stress, whose formation primarily derived from type 1 protein arginine N-methyltransferase (PRMT1) and whose metabolism was governed by type 1 dimethylarginine dimethylaminohydrolase (DDAH1). This study aimed to evaluate participation of the PRMT1-ADMA-DDAH1 metabolism axis in the kidneys of type 2 diabetes model rats and human subjects, and the effect of probucol on this axis and renal function.

Methods: A total of 30 rats were randomly assigned to a normal group (NC, n=10), diabetic group (DM, n=10), and a diabetics under probucol treatment group (PM, n=10). Throughout 8 weeks of probucol treatment, plasma NOS, the malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), and catalase (CAT) activity were evaluated by chemical colorimetric approach. ADMA concentration was evaluated with an enzyme-linked immunosorbent assay (ELISA) and analysis of expression of PRMT1 and DDAH1 in kidneys with reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry (IHC) and western blotting were performed.

Results: The expression of DDAH1 in the kidney, and the plasma NOS, NO, SOD, and CAT activities in diabetic group were lower, while MDA and the expression of PRMT1 and ADMA were higher in contrast to the control group. In diabetics rats receiving probucol, the expressions of DDAH1 and ADMA were downregulated, whereas that of PRMT1 was upregulated. Probucol inhibited the indexes of oxidative stress and improved the kidney function in both diabetic rats and humans.

Conclusions: We found that the expression of the PRMT1-ADMA-DDAH1 axis was altered in the kidneys of diabetic rats. Moreover, results indicated that probucol therapy regulates expression at both ends of this axis, which may preserve renal function by reducing oxidant stress. Therefore, probucol may partially restore expression of the PRMT1-ADMA-DDAH1 axis in diabetic kidneys, immigrate oxidant stress, and enhance renal function.
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http://dx.doi.org/10.21037/apm-21-417DOI Listing
March 2021

Microcystin-LR inhibits testosterone synthesis via reactive oxygen species-mediated GCN2/eIF2α pathway in mouse testes.

Sci Total Environ 2021 Mar 25;781:146730. Epub 2021 Mar 25.

Department of Toxicology & Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University, Hefei 230032, China. Electronic address:

Previous studies demonstrated that microcystin-leucine-arginine (MC-LR) disrupted testosterone (T) synthesis, but the underlying mechanisms are not entirely elucidated. This study aims to explore the role of reactive oxygen species (ROS)-mediated GCN2/eIF2α activation on MC-LR-induced disruption of testicular T synthesis. Male mice were intraperitoneally injected with MC-LR (0 or 20 μg/kg) daily for 5 weeks. Serum T was decreased in MC-LR-exposed mice (0.626 ± 0.122 vs 24.565 ± 8.486 ng/ml, P < 0.01), so did testicular T (0.667 ± 0.15 vs 8.317 ± 1.387 ng/mg protein, P < 0.01). Steroidogenic proteins including StAR, CYP11A1 and CYP17A1 were downregulated in MC-LR-exposed mouse testes and TM3 cells. Mechanistically, p-GCN2 and p-eIF2α were elevated in MC-LR-exposed TM3 cells. GCN2iB attenuated MC-LR-induced GCN2 and eIF2α phosphorylation in TM3 cells. Moreover, GCN2iB attenuated MC-LR-induced downregulation of steroidogenic proteins in TM3 cells. Further analysis found that cellular ROS were elevated and HO-1 was upregulated in MC-LR-exposed TM3 cells. PBN rescued MC-LR-induced activation of GCN2/eIF2α signaling in TM3 cells. Additionally, pretreatment with PBN attenuated MC-LR induced downregulation of steroidogenic proteins and synthases in TM3 cells. These results suggest that ROS-mediated GCN2/eIF2α activation contributes partially to MC-LR-caused downregulation of steroidogenic proteins and synthases. The present study provides a new clue for understanding the mechanism of MC-LR-induced endocrine disruption.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146730DOI Listing
March 2021

Recurrence characteristics and clinicopathological results of borderline ovarian tumors.

BMC Womens Health 2021 Mar 31;21(1):134. Epub 2021 Mar 31.

Department of Gynecology, First Hospital of Shanxi Medical University, NO.85 South Jiefang Road, Yingze District, Taiyuan, 030001, China.

Background: This study aimed to investigate the clinical and pathological characteristics, and the recurrence and prognostic factors of borderline ovarian tumors (BOTs).

Methods: The data of 286 patients admitted to hospital and followed up for more than ten months were analyzed retrospectively to study the clinicopathological characteristics and related factors of recurrence.

Results: The median age of the patients was 42.06 ± 14.97 years, and the duration of the follow-up ranged from 10-109 months. During the follow-up period, 40 patients had a recurrence. Of these patients, 36 were ≤ 40 years, and patients with premenopausal recurrence accounted for 20.5% (36/176). In patients undergoing conservative treatment or radical operations, the recurrence rates were 21.3% and 1.8%, respectively, and they were 13.4% (36/268) in patients at Federation International of Gynecology and Obstetrics (FIGO) stage I, and 22.2% (4/18) in patients at an advanced stage. Postoperative pathology revealed that 40 patients had micropapillary tumors, among whom ten patients (25%) had a recurrence, and 19 patients had complications with interstitial infiltration. Of these 19 patients, six had a recurrence (31.5%). Another 22 patients had complications with calcified sand bodies; among these, eight patients (36.4%) had a recurrence. All the differences were statistically significant (P < 0.05). There were four cancer-related deaths during the follow-up period. Late FIGO stage, conservative operation, and a high level of carbohydrate antigen 125 (CA125) were independent risk factors for the recurrence of BOTs.

Conclusion: BOTs usually occur in women under 40 years, have an occult onset, and half of the patients have no obvious clinical manifestations. Serum CA125 level can be used as a tumor marker to detect BOTs and the risk of its recurrence. Operation mode and FIGO stage are important independent factors for the recurrence of BOTs.
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http://dx.doi.org/10.1186/s12905-021-01263-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011410PMC
March 2021

Controlling Nutritional Status score predict the individualized survival of patients with gastric cancer.

Asia Pac J Clin Nutr 2021 ;30(1):51-59

Oncology Department, Peking University, First Hospital, Beijing, China. Email:

Background And Objectives: The present study aimed to determine the correlation between Controlling Nutritional Status (CONUT) score and prognosis in gastric cancer patients undergoing total gastrectomy.

Methods And Study Design: The clinical data of 245 gastric cancer patients who underwent total gastrectomy in Peking University, First Hospital between January1st 2005 and December 30th 2015 were retrospectively collected. According to the CONUT level, they were divided into high CONUT (>3) group and low CONUT (≤3) group. The relationship between CONUT and the disease-free survival (DFS) and overall survival (OS) were analyzed by statistical analysis.

Results: The results showed that the optimal cutoff value for CONUT to predict the 5-year survival was 3 and CONUT had a higher area under the ROC curve (AUC) for 5-year disease free survival (DFS) and overall survival (OS) prediction. Additionally, when age was considered as a stratified factor, univariate analyses demonstrated that high CONUT correlated with shorter DFS in non-elderly (<65) patients and shorter DFS and OS in elderly (≥65) patients.

Conclusions: High CONUT was significantly correlated with older age, advanced TNM-stage, higher Ki-67 and pathological subtype. Patients with high pre-operative high CONUT levels should be given more observation and constant follow-up after surgery.
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http://dx.doi.org/10.6133/apjcn.202103_30(1).0007DOI Listing
January 2021

Exploration of an Integrative Prognostic Model of Radiogenomics Features With Underlying Gene Expression Patterns in Clear Cell Renal Cell Carcinoma.

Front Oncol 2021 8;11:640881. Epub 2021 Mar 8.

School of Bioscience and Technology, Chengdu Medical College, Chengdu, China.

Background: Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies in urinary system, and radiomics has been adopted in tumor staging and prognostic evaluation in renal carcinomas. This study aimed to integrate image features of contrast-enhanced CT and underlying genomics features to predict the overall survival (OS) of ccRCC patients.

Method: We extracted 107 radiomics features out of 205 patients with available CT images obtained from TCIA database and corresponding clinical and genetic information from TCGA database. LASSO-COX and SVM-RFE were employed independently as machine-learning algorithms to select prognosis-related imaging features (PRIF). Afterwards, we identified prognosis-related gene signature through WGCNA. The random forest (RF) algorithm was then applied to integrate PRIF and the genes into a combined imaging-genomics prognostic factors (IGPF) model. Furthermore, we constructed a nomogram incorporating IGPF and clinical predictors as the integrative prognostic model for ccRCC patients.

Results: A total of four PRIF and four genes were identified as IGPF and were represented by corresponding risk score in RF model. The integrative IGPF model presented a better prediction performance than the PRIF model alone (average AUCs for 1-, 3-, and 5-year were 0.814 0.837, 0.74 0.806, and 0.689 0.751 in test set). Clinical characteristics including gender, TNM stage and IGPF were independent risk factors. The nomogram integrating clinical predictors and IGPF provided the best net benefit among the three models.

Conclusion: In this study we established an integrative prognosis-related nomogram model incorporating imaging-genomic features and clinical indicators. The results indicated that IGPF may contribute to a comprehensive prognosis assessment for ccRCC patients.
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http://dx.doi.org/10.3389/fonc.2021.640881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982462PMC
March 2021

Heat Shock Protein 90 Triggers Multi-Drug Resistance of Ovarian Cancer via AKT/GSK3β/β-Catenin Signaling.

Front Oncol 2021 2;11:620907. Epub 2021 Mar 2.

School of Bioscience and Technology, Chengdu Medical College, Chengdu, China.

Ovarian cancer is the most lethal gynaecologic tumor, with which multi-drug resistance as the major therapeutic hindrance. Heat shock protein 90 (Hsp90) has been involved in cancer malignant behaviors. However, its role and mechanism in multi-drug resistance of ovarian cancer remains poorly understood. Our results demonstrated that Hsp90 was overexpressed in multi-drug resistant ovarian cancer cells. Hsp90 downregulation by shHsp90 or inhibitor BIIB021 increased the sensitivity of multi-drug resistant ovarian cancer cells to paclitaxel and cisplatin, and augmented the drugs-induced apoptosis. Hsp90 positively regulated the expressions of multi-drug resistance protein 1 (P-gp/MDR1), breast cancer resistance protein (BCRP), Survivin and Bcl-2 expressions closely associated with multi-drug resistance. Moreover, overexpression of Hsp90 promoted β-catenin accumulation, while Hsp90 downregulation decreased the accumulation, nuclear translocation and transcriptional activity of β-catenin. We also identified that β-catenin was responsible for Hsp90-mediated expressions of P-gp, BCRP, Survivin, and Bcl-2. Furthermore, Hsp90 enhanced the AKT/GSK3β signaling, and AKT signaling played a critical role in Hsp90-induced accumulation and transcriptional activity of β-catenin, as well as multi-drug resistance to paclitaxel and cisplatin. In conclusion, Hsp90 enhanced the AKT/GSK3β/β-catenin signaling to induce multi-drug resistance of ovarian cancer. Suppressing Hsp90 chemosensitized multi-drug resistant ovarian cancer cells via impairing the AKT/GSK3β/β-catenin signaling, providing a promising therapeutic strategy for a successful treatment of ovarian cancer.
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http://dx.doi.org/10.3389/fonc.2021.620907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960917PMC
March 2021

The furin-S2' site in avian coronavirus plays a key role in central nervous system damage progression.

J Virol 2021 Mar 16. Epub 2021 Mar 16.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China

The furin cleavage site plays an important role in virus pathogenicity. The spike protein of SARS-CoV-2 harbors a furin cleavage site insertion in contrast to SARS-CoV, which may be related to its stronger communicability. An avian coronavirus with an extra furin cleavage site upstream of the fusion peptide (S2' site) infected monocyte cells and neuron cells leading to viremia or encephalitis, respectively. Immunohistochemistry and real-time quantitative polymerase chain reaction were used to follow disease progression and demonstrated differences between the parent avian coronavirus and mutated avian coronavirus with a furin-S2' site. Magnetic resonance imaging and biological dye to evaluate the blood-brain barrier permeability showed that avian coronavirus with a furin-S2' site had increased permeability compared with parent avian coronavirus. Immunohistochemistry of brains after intracerebral injection of avian coronavirus and immunofluorescence staining of primary neuron cells demonstrated the furin-S2' site expanded the cell tropism of the mutant avian coronavirus to neuron cells. TNF-α, which has a key role in blood-brain barrier permeability, was highly induced by avian coronavirus with a furin-S2' site compared with the parent avian coronavirus. We demonstrated the process involved in mutant avian coronavirus-induced disease and that the addition of a furin-S2' site changed the virus cell tropism.Coronaviruses have broken out three times in two decades. Spike (S) protein plays a key role in the process of infection. To clarify importance of furin cleavage site in spike protein for coronavirus, we investigated the pathogenesis of neurotropic avian coronavirus whose spike protein contains an extra furin cleavage site (furin-S2' site). By combining real-time quantitative polymerase chain reaction and immunohistochemistry we demonstrated that infectious bronchitis virus (IBV) infects brain instead of trachea when its S protein contains furin-S2' site. Moreover, the virus was shown to increase the permeability of blood-brain barrier, infect neuron cells and induce high expression of TNF-α. Based on these results we further show that furin cleavage site in S protein plays an important role in coronavirus pathogenicity and cell tropism. Our study extends previous publications on function of S protein of coronavirus, increasing the understanding of researchers to coronavirus.
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http://dx.doi.org/10.1128/JVI.02447-20DOI Listing
March 2021

Biochemical characterization of a unique DNA polymerase A from the extreme radioresistant organism Deinococcus radiodurans.

Biochimie 2021 Mar 13;185:22-32. Epub 2021 Mar 13.

The MOE Key Laboratory of Biosystems Homeostasis & Protection, Institute of Biophysics, College of Life Sciences, Zhejiang University, China. Electronic address:

Deinococcus radiodurans survives extraordinary doses of ionizing radiation and desiccation that cause numerous DNA strand breaks. D. radiodurans DNA polymerase A (DrPolA) is essential for reassembling the shattered genome, while its biochemical property has not been fully demonstrated. In this study, we systematically examined the enzymatic activities of DrPolA and characterized its unique features. DrPolA contains an N-terminal nuclease domain (DrPolA-NTD) and a C-terminal Klenow fragment (KlenDr). Compared with the Klenow fragment of E. coli Pol I, KlenDr shows higher fidelity despite the lacking of 3'-5' exonuclease proofreading activity and prefers double-strand DNA rather than Primer-Template substrates. Apart from the well-annotated 5'-3' exonuclease and flap endonuclease activities, DrPolA-NTD displays approximately 140-fold higher gap endonuclease activity than its homolog in E. coli and Human FEN1. Its 5'-3' exonuclease activity on ssDNA, gap endonuclease, and Holliday junction cleavage activities are greatly enhanced by Mn. The DrPolA-NTD deficient strain shows increased sensitivity to UV and gamma-ray radiation. Collectively, our results reveal distinct biochemical characteristics of DrPolA during DNA degradation and re-synthesis, which provide new insight into the outstanding DNA repair capacity of D. radiodurans.
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http://dx.doi.org/10.1016/j.biochi.2021.02.014DOI Listing
March 2021

Classifying crime places by neighborhood visual appearance and police geonarratives: a machine learning approach.

J Comput Soc Sci 2021 Mar 8:1-25. Epub 2021 Mar 8.

Texas A & M University, College Station, USA.

The complex interrelationship between the built environment and social problems is often described but frequently lacks the data and analytical framework to explore the potential of such a relationship in different applications. We address this gap using a machine learning (ML) approach to study whether street-level built environment visuals can be used to classify locations with high-crime and lower-crime activities. For training the ML model, spatialized expert narratives are used to label different locations. Semantic categories (e.g., road, sky, greenery, etc.) are extracted from Google Street View (GSV) images of those locations through a deep learning image segmentation algorithm. From these, local visual representatives are generated and used to train the classification model. The model is applied to two cities in the U.S. to predict the locations as being linked to high crime. Results show our model can predict high- and lower-crime areas with high accuracies (above 98% and 95% in first and second test cities, accordingly).
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http://dx.doi.org/10.1007/s42001-021-00107-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938887PMC
March 2021

Effect of Dexmedetomidine Hydrochloride on perioperative inflammation and postoperative lung infection in patients with spinal tuberculosis.

Pak J Med Sci 2021 Mar-Apr;37(2):520-524

Hong-xun Cui, Department of Orthopedics, Orthopedic Hospital of Henan Province, Luoyang, Henan 471000, P.R. China.

Objective: To explore the effect of dexmedetomidine hydrochloride on perioperative inflammation and postoperative lung infection in patients with spinal tuberculosis.

Method: A double-blind control observation was conducted in spinal tuberculosis patients with the use of general anesthesia during the operation. A total of 171 spinal tuberculosis patients who received endotracheal intubation for general anesthesia in Henan University of Chinese Medicine from January 2017 to April 2019 were included. The concentration changes in serum TNF-α and IL-6 were recorded at one hour, six hour and one day after the operation. The incidence of postoperative pulmonary complications of patients were also evaluated.

Results: The results showed that in the experimental group compared with the control group, serum TNF-α and IL-6 concentrations one hour, six hour and one day after the operation were significantly lower (P<0.05). The rate of postoperative pulmonary complications was lower in the experimental group than that in the control group (P<0.05).

Conclusion: Dexmedetomidine hydrochloride has obvious anti-inflammatory effects and can reduce the incidence of pulmonary complications after surgery.
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http://dx.doi.org/10.12669/pjms.37.2.2383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931321PMC
March 2021

MazEF Toxin-Antitoxin System-Mediated DNA Damage Stress Response in .

Front Genet 2021 19;12:632423. Epub 2021 Feb 19.

Institute of Biophysics, College of Life Sciences, Zhejiang University, Hangzhou, China.

shows marked resistance to various types of DNA-damaging agents, including mitomycin C (MMC). A type II toxin-antitoxin (TA) system that responds to DNA damage stress was identified in , comprising the toxin MazF-dr and the antitoxin MazE-dr. The cleavage specificity of MazF-dr, an endoribonuclease, was previously characterized. Here, we further investigated the regulatory role of the MazEF system in the response to DNA damage stress in . The crystal structure of MazF (MazF-dr) was determined at a resolution of 1.3 Å and is the first structure of the toxin of the TA system of . MazF-dr forms a dimer mediated by the presence of interlocked loops. Transcriptional analysis revealed 650 downregulated genes in the wild-type (WT) strain, but not in the mutant strain, which are potentially regulated by MazEF-dr in response to MMC treatment. Some of these genes are involved in membrane trafficking and metal ion transportation. Subsequently, compared with the WT strain, the mutant strain exhibited much lower MMC-induced intracellular iron concentrations, reactive oxygen species (ROS), and protein carbonylation levels. These results provide evidence that MazEF-mediated cell death in might be caused by an increase in ROS accumulation upon DNA damage stress.
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http://dx.doi.org/10.3389/fgene.2021.632423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933679PMC
February 2021

An attenuated TW-like infectious bronchitis virus strain has potential to become a candidate vaccine and S gene is responsible for its attenuation.

Vet Microbiol 2021 Mar 17;254:109014. Epub 2021 Feb 17.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. Electronic address:

TW-like infectious bronchitis virus (IBV) with high pathogenicity is becoming the predominant IBV type circulating in China. To develop vaccines against TW-like IBV strains and investigate the critical genes associated with their virulence, GD strain was attenuated by 140 serial passages in specific-pathogen-free embryonated eggs and the safety and efficacy of the attenuated GD strain (aGD) were examined. The genome sequences of GD and aGD were also compared and the effects of mutations in the S gene were observed. The results revealed that aGD strain showed no obvious pathogenicity with superior protective efficacy against TW-like and QX-like virulent IBV strains. The genomes of strains aGD and GD shared high similarity (99.87 %) and most of the mutations occurred in S gene. Recombinant IBV strain rGD, in which the S gene was replaced with the corresponding regions from aGD, showed decreased pathogenicity compared with its parental strain. In conclusion, attenuated TW-like IBV strain aGD is a potential vaccine candidate and the S gene is responsible for its attenuation. Our research has laid the foundation for future exploration of the attenuating molecular mechanism of IBV.
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http://dx.doi.org/10.1016/j.vetmic.2021.109014DOI Listing
March 2021

Long non‑coding RNA suppresses ovarian cancer progression by regulating Hippo/YAP signaling.

Int J Mol Med 2021 Apr 12;47(4). Epub 2021 Feb 12.

Department of Gynecology and Obstetrics, The China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130000, P.R. China.

Long non‑coding RNAs (lncRNAs) are a class of non‑protein coding transcripts that are involved in the regulation of gene expression in mammalian cells. Transcriptional co‑activator Yes associated protein 1 (YAP1) plays a key role in the progression of ovarian cancer. However, the regulation of Hippo/YAP signaling in ovarian cancer remains elusive. In the present study, the expression levels of lncRNA were investigated. The analysis indicated that lncRNA expression was downregulated in ovarian tumor samples and ovarian cancer cells. The overexpression of inhibited ovarian cancer cell proliferation and induced cell apoptosis. Bioinformatics analysis predicted that miR‑2278, a previously reported upregulated miRNA in ovarian tumors, may bind to . Dual luciferase assay confirmed the direct regulatory association between and miR‑2278. In addition, the data demonstrated that large tumor suppressor 2 (LATS2) was a target gene of miR‑2278, whose expression was upregulated by in ovarian cancer cells. By regulating the expression of LATS2, induced the downregulation of YAP1 expression in ovarian cancer cells. Moreover, the silencing of LATS2 attenuated the inhibition of cell proliferation and the apoptosis induced by overexpression in ovarian cancer cells. The association among the expression levels of , miR‑2278 and LATS2 was observed in specimens obtained from patients with ovarian cancer. Taken together, the data presented herein demonstrate that functions as a potential tumor suppressor lncRNA by upregulating LATS2 expression in ovarian cancer.
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http://dx.doi.org/10.3892/ijmm.2021.4877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895538PMC
April 2021

USP9X-mediated KDM4C deubiquitination promotes lung cancer radioresistance by epigenetically inducing TGF-β2 transcription.

Cell Death Differ 2021 Feb 8. Epub 2021 Feb 8.

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

Radioresistance is regarded as the main barrier to effective radiotherapy in lung cancer. However, the underlying mechanisms of radioresistance remain elusive. Here, we show that lysine-specific demethylase 4C (KDM4C) is overexpressed and correlated with poor prognosis in lung cancer patients. We provide evidence that genetical or pharmacological inhibition of KDM4C impairs tumorigenesis and radioresistance in lung cancer in vitro and in vivo. Moreover, we uncover that KDM4C upregulates TGF-β2 expression by directly reducing H3K9me3 level at the TGF-β2 promoter and then activates Smad/ATM/Chk2 signaling to confer radioresistance in lung cancer. Using tandem affinity purification technology, we further identify deubiquitinase USP9X as a critical binding partner that deubiquitinates and stabilizes KDM4C. More importantly, depletion of USP9X impairs TGF-β2/Smad signaling and radioresistance by destabilizing KDM4C in lung cancer cells. Thus, our findings demonstrate that USP9X-mediated KDM4C deubiquitination activates TGF-β2/Smad signaling to promote radioresistance, suggesting that targeting KDM4C may be a promising radiosensitization strategy in the treatment of lung cancer.
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http://dx.doi.org/10.1038/s41418-021-00740-zDOI Listing
February 2021

Dietary betaine prevents obesity through gut microbiota-drived microRNA-378a family.

Gut Microbes 2021 Jan-Dec;13(1):1-19

College of Animal Science and Technology, Sichuan Agricultural University , Chengdu, China.

Betaine is a natural compound present in commonly consumed foods and may have a potential role in the regulation of glucose and lipids metabolism. However, the underlying molecular mechanism of its action remains largely unknown. Here, we show that supplementation with betaine contributes to improved high-fat diet (HFD)-induced gut microbiota dysbiosis and increases anti-obesity strains such as , and . In mice lacking gut microbiota, the functional role of betaine in preventing HFD-induced obesity, metabolic syndrome, and inactivation of brown adipose tissues are significantly reduced. is an important regulator of betaine in improving microbiome ecology and increasing strains that produce short-chain fatty acids (SCFAs). Increasing two main members of SCFAs including acetate and butyrate can significantly regulate the levels of DNA methylation at host miR-378a promoter, thus preventing the development of obesity and glucose intolerance. However, these beneficial effects are partially abolished by Yin yang (YY1), a common target gene of the miR-378a family. Taken together, our findings demonstrate that betaine can improve obesity and associated MS via the gut microbiota-derived miR-378a/YY1 regulatory axis, and reveal a novel mechanism by which gut microbiota improve host health.
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http://dx.doi.org/10.1080/19490976.2020.1862612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889173PMC
February 2021

Honokiol induces paraptosis-like cell death of acute promyelocytic leukemia via mTOR & MAPK signaling pathways activation.

Apoptosis 2021 Apr 7;26(3-4):195-208. Epub 2021 Feb 7.

Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People's Republic of China.

Acute promyelocytic leukemia (APL) is a blood system disease caused by the accumulation of a large number of immature blood cells in bone marrow. Although the introduction of all-trans retinoic acid (ATRA) and arsenic has reached a high level of complete remission rate and 5-year disease-free survival rate, the occurrence of various adverse reactions still severely affects the quality of life of patients. As a natural product, honokiol (HNK) has the advantages of low toxicity and high efficiency, and it is a potential drug for the treatment of cancer. Since cancer cells can escape apoptotic cell death through multiple adaptive mechanisms, HNK, a drug that induces cancer cell death in a nonapoptotic way, has attracted much interest. We found that HNK reduced the viability of human APL cell line (NB4 cells) by inducing paraptosis-like cell death. The process was accompanied by excessive reactive oxygen species (ROS), mitochondrial damage, endoplasmic reticulum stress, and increased microtubule-associated protein 1 light chain 3 (LC3) processing. The inactivation of proteasome activity was the main cause of misfolded and unfolded protein accumulation in endoplasmic reticulum, such as LC3II/I and p62. This phenomenon could be alleviated by adding cycloheximide (CHX), a protein synthesis inhibitor. We found that mTOR signaling pathway participated in paraptosis-like cell death induced by HNK in an autophagy-independent process. Moreover, the mitogen-activated protein kinase (MAPK) signaling pathway induced paraptosis of NB4 cells by promoting endoplasmic reticulum stress. In summary, these findings indicate that paraptosis may be a new way to treat APL, and provide novel insights into the potential mechanism of paraptosis-like cell death.
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http://dx.doi.org/10.1007/s10495-020-01655-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016806PMC
April 2021

LncRNA ANRIL Regulates Ovarian Cancer Progression and Tumor Stem Cell-Like Characteristics via miR-324-5p/Ran Axis.

Onco Targets Ther 2021 19;14:565-576. Epub 2021 Jan 19.

Department of Gynaecology and Obstetrics, The Third Hospital of Jilin University, Changchun, Jilin 130000, People's Republic of China.

Objective: Long non-coding RNA (lncRNA) ANRIL is emerging as a crucial role in ovarian cancer progression and prognosis. However, the precise molecular mechanism of ANRIL on ovarian cancer is not known. Thus, we aim to study the underlying mechanism of ANRIL on the action.

Methods: The MTT assay assessed cell viability. Cell migration and invasion were determined using the wound healing assay, Transwell migration, and invasion assay. The relationships of ANRIL, miR-324-5p, and RAN were evaluated using luciferase activity assay and RNA pull-down assay. Cancer stem cell was identified by flow cytometry. Sphere formation assay was conducted to determine the stem-like properties. Xenograft tumor was established to assess tumor growth in vivo. qRT-PCR and Western blot were used to detect gene expression.

Results: ANRIL was elevated while miR-324-5p was decreased in ovarian cancer tissues and cells. Besides, downregulated ANRIL enhanced miR-324-5p expression, and the luciferase reporting experiment and RNA pull-down assay showed the binding interaction between ANRIL and miR-324-5p. miR-324-5p directly targeted Ran and negatively modulated the expression of Ran. Besides, Ran was promoted by overexpressed ANRIL, which was reversed by overexpression of miR-324-5p. Furthermore, decreased ANRIL and increased miR-324-5p suppressed tumor growth, migration capacity, drug resistance, and alleviated stem-like characteristics in vitro and in vivo. Ran mediated the regulation of ANRIL on cell viability, stem-like properties, and drug resistance of ovarian cancer cells.

Conclusion: The ANRIL/miR-324-5p/Ran axis regulated ovarian cancer development, making the axis meaningful targets for ovarian cancer therapy.
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http://dx.doi.org/10.2147/OTT.S273614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826075PMC
January 2021

Application of Conchal Cartilage Grafts in Nasal Tip Plasty: Comparison and Experience of 3 Methods.

Ann Plast Surg 2021 03;86(3S Suppl 2):S199-S207

From the Department of Plastic and Reconstructive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China.

Introduction: The autologous conchal cartilage of good elasticity is easy to harvest, thus is often used in nasal tip plasty of East Asians. However, the operation techniques vary a lot among different surgeons. This article aims to introduce 3 techniques commonly used in clinical practice.

Methods: One hundred three patients were included in this study and divided into 3 groups according to the shape of the nasal tip during 2017 to 2019. The patients were followed up for at least 6 months. All patients were measured with Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS). ImageJ software was used to measure and calculate the projection ratio for lateral position standard image, and columella-labial angle (CLA) was measured.

Results: In group 1, SCHNOS for nasal obstruction (SCHNOS-O) score were 13.23 ± 7.61 and 14.49 ± 10.55 (P > 0.05); SCHNOS for nasal cosmesis (SCHNOS-C) score were 66.55 ± 31.23 and 21.73 ± 18.91 (P < 0.001); projection ratio were 0.51 ± 0.04 and 0.57 ± 0.05 (P < 0.001); CLA were 91.02° ± 5.67° and 93.55° ± 4.64° (P > 0.05), preoperative and postoperative, respectively. In group 2, SCHNOS-O score were 16.76 ± 13.44 and 15.44 ± 9.26 (P > 0.05); SCHNOS-C score were 61.87 ± 44.14 and 19.16 ± 29.37 (P < 0.001); projection ratio were 0.50 ± 0.05 and 0.58 ± 0.03 (P < 0.001); CLA were 92.32° ± 6.39° and 94.86° ± 5.96°(P > 0.05), preoperative and postoperative, respectively. In group 3, SCHNOS-O score were 15.25 ± 7.83 and 17.73 ± 11.66 (P > 0.05); SCHNOS-C score were 52.03 ± 33.38 and 17.73 ± 11.66 (P < 0.001); projection ratio were 0.53 ± 0.05 and 0.57 ± 0.02 (P < 0.001); CLA were 91.65° ± 5.75° and 93.21° ± 5.38° (P > 0.05), preoperational and postoperational, respectively.

Conclusions: None of these 3 techniques cause or aggravate nasal obstruction, and all of them can achieve high cosmetic satisfaction. Technique 1 and technique 2 are suitable for the patients with moderate and moderate to severe short nose that is common in East Asia, which can better increase the protrusion of the tip and length of the nose. Technique 3 is suitable for the patients with better shape of the nose, who need to slightly increase the protrusion of the nasal tip and increase the upward rotation.
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http://dx.doi.org/10.1097/SAP.0000000000002638DOI Listing
March 2021

Radiation exposure triggers the malignancy of non‑small cell lung cancer cells through the activation of visfatin/Snail signaling.

Oncol Rep 2021 Mar 8;45(3):1153-1161. Epub 2021 Jan 8.

Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.

It is estimated that one‑half of patients with non‑small cell lung cancer (NSCLC) undergo radiotherapy worldwide. However, the outcome of radiotherapy alone is not always satisfactory. The aim of the present study was to evaluate the effects of radiotherapy on the malignancy of NSCLC cells. It was demonstrated that radiation therapy could increase the migration and invasion of NSCLC cells in vitro. Moreover, the upregulation of visfatin, a 52‑kDa adipokine, mediated radiation‑induced cell motility. A neutralizing antibody specific for visfatin blocked radiation‑induced cell migration. Radiation and visfatin induced the expression of Snail, a key molecule that regulates epithelial to mesenchymal transition in NSCLC cells. Furthermore, visfatin positively regulated the mRNA stability of Snail in NSCLC cells, but had no effect on its protein degradation. This may be explained by visfatin‑mediated downregulation of microRNA (miR)‑34a, which was shown to bind the 3' untranslated region of Snail mRNA to promote its decay. Collectively, these findings suggested that radiation could induce cell motility in NSCLC cells through visfatin/Snail signaling.
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http://dx.doi.org/10.3892/or.2021.7929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859998PMC
March 2021

Profiling and Functional Analysis of Long Noncoding RNAs and mRNAs during Porcine Skeletal Muscle Development.

Int J Mol Sci 2021 Jan 6;22(2). Epub 2021 Jan 6.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.

Gene transcripts or mRNAs and long noncoding RNAs (lncRNAs) are differentially expressed during porcine skeletal muscle development. However, only a few studies have been conducted on skeletal muscle transcriptome in pigs based on timepoints according to the growth curve for porcine. Here, we investigated gene expression in Qingyu pigs at three different growth stages: the inflection point with the maximum growth rate (MGI), the inflection point of the gradually increasing stage to the rapidly increasing stage (GRI), and the inflection point of the rapidly increasing stage to the slowly increasing stage (RSI). Subsequently, we explored gene expression profiles during muscle development at the MGI, GRI and RSI stages by Ribo-Zero RNA sequencing. Qingyu pigs reached the MGI, GRI and RSI stages at 156.40, 23.82 and 288.97 days of age with 51.73, 3.14 and 107.03 kg body weight, respectively. A total of 14,530 mRNAs and 11,970 lncRNAs were identified at the three stages, and 645, 323 differentially expressed genes (DEGs) and 696, 760 differentially expressed lncRNAs (DELs) were identified in the GRI vs. MGI, and RSI vs. MGI, comparisons. Functional enrichment analysis revealed that genes involved in immune system development and energy metabolism (mainly relate to amino acid, carbohydrate and lipid) were enriched at the GRI and MGI stages, respectively, whereas genes involved in lipid metabolism were enriched at the RSI stage. We further characterized , an abundant lncRNA. The full-length sequence (316 nt) of lncRNA was determined by rapid amplification of cDNA ends (RACE). Subcellular distribution analysis by quantitative real-time PCR (qRT-PCR) revealed that is a cytoplasmic lncRNA. Binding site prediction and dual luciferase assay showed that lncRNA directly binds to microRNA 133a (miR-133a). Our findings provide the basis for further investigation of the regulatory mechanisms and molecular genetics of muscle development in pigs.
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http://dx.doi.org/10.3390/ijms22020503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825455PMC
January 2021

Coronavirus Endoribonuclease Ensures Efficient Viral Replication and Prevents Protein Kinase R Activation.

J Virol 2020 Dec 23. Epub 2020 Dec 23.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.

Coronavirus (CoV) nsp15 is an endoribonuclease conserved throughout the CoV family. The enzymatic activity and crystal structure of infectious bronchitis virus (IBV) nsp15 are undefined, and the protein's role in replication remains unclear. We verified the uridylate-specific endoribonuclease (EndoU) activity of IBV and found that the EndoU active sites were located in the C-terminus of nsp15 and included His223, His238, Lys278 and Tyr334. We further constructed an infectious clone of the IBV-rSD strain (rSD-wild-type [WT]) and EndoU-deficient IBVs by changing the codon for the EndoU catalytic residues to alanine. Both the rSD-WT and EndoU-deficient viruses propagated efficiently in embryonated chicken eggs. Conversely, EndoU-deficient viral propagation was severely impaired in chicken embryonic kidney cells, which was reflected in the lower viral mRNA accumulation and protein synthesis. After infecting chickens with the parental rSD-WT strain and EndoU-deficient viruses, the EndoU-deficient-virus-infected chickens presented reduced mortality, tissue injury and viral shedding. Coronaviruses can emerge from animal reservoirs into naive host species to cause pandemic respiratory and gastrointestinal diseases with significant mortality in humans and domestic animals. Infectious bronchitis virus (IBV), a γ-coronavirus, infects respiratory, renal and reproductive systems, causing millions of dollars in lost revenue worldwide annually. Mutating the viral endoribonuclease resulted in an attenuated virus and prevented protein kinase R activation. Therefore, EndoU activity is a virulence factor in IBV infections, thus providing an approach for generating live-attenuated vaccine candidates for emerging coronaviruses.
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http://dx.doi.org/10.1128/JVI.02103-20DOI Listing
December 2020

Identification of EMT-Related Gene Signatures to Predict the Prognosis of Patients With Endometrial Cancer.

Front Genet 2020 2;11:582274. Epub 2020 Dec 2.

Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Background: Endometrial cancer (EC) is one of the most common gynecological cancers. Epithelial-mesenchymal transition (EMT) is believed to be significantly associated with the malignant progression of tumors. However, there is no relevant study on the relationship between EMT-related gene (ERG) signatures and the prognosis of EC patients.

Methods: We extracted the mRNA expression profiles of 543 tumor and 23 normal tissues from The Cancer Genome Atlas database. Then, we selected differentially expressed ERGs (DEERGs) among these mRNAs. Next, univariate and multivariate Cox regression analyses were performed to select the ERGs with predictive ability for the prognosis of EC patients. In addition, risk score models were constructed based on the selected genes to predict patients' overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS). Finally, nomograms were constructed to estimate the OS and PFS of EC patients, and pan-cancer analysis was performed to further analyze the functions of a certain gene.

Results: Six OS-, ten PFS-, and five DFS-related ERGs were obtained. By constructing the prognostic risk score model, we found that the OS, PFS, and DFS of the high-risk group were notably poorer. Last, we found that AQP5 appeared in all three gene signatures, and through pan-cancer analysis, it was also found to play an important role in immunity in lower grade glioma (LGG), which may contribute to the poor prognosis of LGG patients.

Conclusions: We constructed ERG signatures to predict the prognosis of EC patients using bioinformatics methods. Our findings provide a thorough understanding of the effect of EMT in patients with EC and provide new targets and ideas for individualized treatment, which has important clinical significance.
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http://dx.doi.org/10.3389/fgene.2020.582274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738567PMC
December 2020

Construction and Validation of a Novel Glycometabolism-Related Gene Signature Predicting Survival in Patients With Ovarian Cancer.

Front Genet 2020 12;11:585259. Epub 2020 Nov 12.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Among all fatal gynecological malignant tumors, ovarian cancer has the highest mortality rate. The purpose of this study was to develop a stable and personalized glycometabolism-related prognostic signature to predict the overall survival of ovarian cancer patients. The gene expression profiles and clinical information of ovarian cancer patients were derived from four public GEO datasets, which were divided into training and testing cohorts. Glycometabolism-related genes significantly associated with prognosis were selected. A risk score model was established and validated to evaluate its predictive value. We found 5 genes significantly related to prognosis and established a five-mRNA signature. The five-mRNA signature significantly divided patients into a low-risk group and a high-risk group in the training set and validation set. Survival analysis showed that high risk scores obtained by the model were significantly correlated with adverse survival outcomes and could be regarded as an independent predictor for patients with ovarian cancer. In addition, the five-mRNA signature can predict the overall survival of ovarian cancer patients in different subgroups. In summary, we successfully constructed a model that can predict the prognosis of patients with ovarian cancer, which provides new insights into postoperative treatment strategies, promotes individualized therapy, and provides potential new targets for immunotherapy.
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http://dx.doi.org/10.3389/fgene.2020.585259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689371PMC
November 2020

Identification of hsa-miR-1275 as a Novel Biomarker Targeting for Human Epilepsy of Unknown Etiology.

Mol Ther Methods Clin Dev 2020 Dec 14;19:398-410. Epub 2020 Oct 14.

School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211800, China.

Epilepsy affects around 70 million people worldwide, with a 65% rate of unknown etiology. This rate is known as epilepsy of unknown etiology (EUE). Dysregulation of microRNAs (miRNAs) is recognized to contribute to mental disorders, including epilepsy. However, miRNA dysregulation is poorly understood in EUE. Here, we conducted miRNA expression profiling of EUE by microarray technology and identified 57 pathogenic changed miRNAs with significance. The data and bioinformatic analysis results indicated that among these miRNAs, hsa-microRNA (miR)-1275 was highly associated with neurological disorders. Subsequently, new samples of serum and cerebrospinal fluid were collected for validation of hsa-miR-1275 expression by TaqMan assays. Results show that hsa-miR-1275 in serums of EUE were increased significantly, but in cerebrospinal fluid, the miRNA was decreased. Moreover, the gene was selected as a hsa-miR-1275 target based on target prediction tools and gene ontology analysis. Validation of tests proved that MECP2 expression was specifically inhibited by hsa-miR-1275. Additionally, overexpression of hsa-miR-1275 can elevate expression of nuclear factor κB (NF-κB) and promote cell apoptosis. Taken together, hsa-miR-1275 might represent a novel biomarker targeting for human EUE.
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http://dx.doi.org/10.1016/j.omtm.2020.10.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677659PMC
December 2020

Hsa_circ_0048179 attenuates free fatty acid-induced steatosis via hsa_circ_0048179/miR-188-3p/GPX4 signaling.

Aging (Albany NY) 2020 11 18;12(23):23996-24008. Epub 2020 Nov 18.

Laboratory for Advanced Interdisciplinary Research, Institutes of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Although circular RNAs (circRNAs) are known to play key roles in non-alcoholic fatty liver disease, much about their targets and mechanisms remains unknown. We therefore investigated the actions and mechanisms of hsa_circ_0048179 in an model of NAFLD. HepG2 cells were exposed to oleate/palmitate (2:1 ratio) for 24 h to induce intracellular lipid accumulation. Using CCK-8 assays, flow cytometry, fluorescence microscopy, western blotting, RT-qPCR, and Oil red O staining, we found that oleate/palmitate treatment reduced cell viability while increasing apoptosis and lipid accumulation in HepG2 cells. Levels of the antioxidant enzyme GPX4 were decreased in oleate/palmitate-treated HepG2 cells, and there were corresponding increases in reactive oxygen species and damage to mitochondrial cristae. Levels of hsa_circ_0048179 expression were also suppressed by oleate/palmitate treatment, and GPX4 levels were markedly increased in HepG2 cells following transfection with hsa_circ_0048179. Analysis of its mechanism revealed that hsa_circ_0048179 upregulated GPX4 levels by acting as a competitive "sponge" of miR-188-3p and that hsa_circ_0048179 attenuated oleate/palmitate-induced lipid accumulation in HepG2 cells by sponging miR-188-3p. Collectively, our findings suggest that hsa_circ_0048179 may play a key role in the pathogenesis of steatosis and may thus be a useful target for drug development.
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http://dx.doi.org/10.18632/aging.104081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762518PMC
November 2020

Integration of transcriptomic, proteomic and metabolomic data to reveal the biological mechanisms of AAI injury in renal epithelial cells.

Toxicol In Vitro 2021 Feb 17;70:105054. Epub 2020 Nov 17.

School of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, PR China. Electronic address:

Overexposure to aristolochic acid I (AAI) can induce aristolochic acid nephropathy (AAN). However, the comprehensive mechanisms of AAI-induced nephrotoxicity have not been entirely explicated. To investigate the toxicological mechanisms by which AAI induces renal injury, human kidney cells (HK-2 cells) were subjected to comprehensive transcriptomic, proteomic and metabolomic analyses. The transcriptomic analysis identified a total of 7749 differentially expressed genes (DEGs) after AAI treatment, while the proteomic analysis found 598 differentially expressed proteins (DEPs) after AAI treatment. The metabolomic analysis revealed 49 and 42 differentially expressed metabolites (DEMs) in the positive and negative ion modes, respectively. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on these DEGs, DEPs and DEMs. The results of the comprehensive analyses of transcripts, proteins, and metabolites indicated that the DEGs, DEPs, and DEMs were jointly regulated in three ways. These genes, proteins and metabolites and their related dysregulated pathways may be promising targets for research on the mechanisms of AAI injury in human renal epithelial cells. This study provides large-scale omics data that can be used to formulate new strategies for the prevention, rapid diagnosis, and treatment of AAI injury.
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http://dx.doi.org/10.1016/j.tiv.2020.105054DOI Listing
February 2021

Low DAPK1 expression correlates with poor prognosis and sunitinib resistance in clear cell renal cell carcinoma.

Aging (Albany NY) 2020 11 16;13(2):1842-1858. Epub 2020 Nov 16.

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

We investigated the prognostic significance of Death-Associated Protein Kinase 1 (DAPK1) and its role in sunitinib resistance in clear cell renal cell carcinoma (ccRCC). DAPK1 mRNA levels were significantly lower in tumor tissues than normal kidney tissues in TCGA-KIRC dataset (n=428). Both overall survival and disease-free survival were significantly shorter in ccRCC patients with low DAPK1 expression than those with high DAPK1 expression. Receiver operating characteristic curve analysis showed that low DAPK1 expression correlated with poor prognosis in ccRCC patients. Multivariate analysis confirmed that DAPK1 expression was an independent prognostic indicator in ccRCC. Gene set enrichment analysis showed that low DAPK1 expression correlates with upregulation of pathways related to metastasis, drug resistance, hypoxia and invasiveness in ccRCC patients. Sunitinib-resistant ccRCC cells show significantly lower DAPK1 mRNA and protein levels than sunitinib-sensitive ccRCC cells. DAPK1 overexpression enhances apoptosis in sunitinib-resistant ccRCC cells via the ATF6-dependent ER stress pathway. Xenograft tumors derived from DAPK1-overxpressing ccRCC cells were significantly smaller than the controls in nude mice. Our finding demonstrates that low DAPK1 expression is an independent prognostic indicator that correlates with ccRCC progression and sunitinib resistance.
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http://dx.doi.org/10.18632/aging.103638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880360PMC
November 2020

LncRNA MALAT1 Promotes Survival of Epithelial Ovarian Cancer Cells by Downregulating miR-145-5p.

Cancer Manag Res 2020 6;12:11359-11369. Epub 2020 Nov 6.

Central Research Room, China-Japan Union Hospital of Jilin University, Changchun 130000, Jilin, People's Republic of China.

Purpose: This paper was aimed at investigating the regulatory mechanism of long non-coding RNA metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) in epithelial ovarian cancer (EOC).

Materials And Methods: MALAT1 and miR-145-5p expression in the tissues, serum, and EOC cell lines (TOV-112D, TOV-21G) of patients with EOC were detected. The two genes were transfected into the cells via upregulating or downregulating their expression. Levels of apoptosis-related proteins (Caspase-3, Bax, Bcl-2) were analyzed. Mechanisms of cell proliferation, invasion, and apoptosis were studied.

Results: MALAT1 was high expressed in EOC tissues, while miR-145-5p was poorly expressed in them. The areas under the curves (AUCs) of the two genes for diagnosing EOC were greater than 0.850, and the two had a significantly negative correlation. According to multivariate Cox regression analysis, high MALAT1 expression, tumor size, degree of differentiation, case staging, and lymph node metastasis were the independent risk factors affecting prognosis. The 5-year overall survival rate (OSR) of patients with low MALAT1 expression was remarkably higher than that of those with high expression. Overexpressing miR-145-5p and silencing MALAT1 could inhibit EOC cells from proliferating and invading, increase their apoptotic rate, and improve levels of the apoptosis-related proteins. After co-transfection with MALAT1-inhibitor + miR-145-5p-inhibitor, the proliferation and invasion of TOV-112D and TOV-21G cells were inhibited and the apoptotic rate rose more obviously. Inhibiting MALAT1 could increase miR-145-5p expression, thus inhibiting EOC cells from proliferating and invading and thereby increasing their apoptotic rate.

Conclusion: MALAT1 promotes EOC cells' survival by downregulating miR-145-5p so it may become a new direction for EOC diagnosis and gene therapy.
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http://dx.doi.org/10.2147/CMAR.S267355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654532PMC
November 2020

Incidence of postoperative sore throat after using a new technique of insertion of a second generation Laryngeal Mask Airway: A randomised controlled trial.

Eur J Anaesthesiol 2021 03;38(3):285-293

From the Jiangsu Province Key laboratory of Anaesthesiology, Xuzhou Medical University (XLi, XiuW, YZ, ZJ, XLv, XN, TL, XinW, SL), the Department of Anaesthesiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou (LD, SL), the Department of Anaesthesiology, Dushuhu Public Hospital Affiliated to Soochow University, Suzhou (XiuW), the Department of Anaesthesiology, Changzhou Maternal and Child Healthcare Hospital, Changzhou (YZ), the Department of Anaesthesiology, Suqian First Hospital, Suqian, Jiangsu, China (LD).

Background: Sore throat is a common complication after Laryngeal Mask Airway Supreme (SLMA) insertion.

Objective: The aim of this study was to determine whether a new SLMA insertion technique (not removing the pilot tube blocker before insertion) lowers the incidence of sore throat in the postanaesthesia care unit (PACU).

Design: A prospective, single-centre, parallel randomised controlled trial.

Setting: Operating room and PACU at a hospital in China from June to September 2019.

Patients: Four hundred and eight patients aged 18 to 65 years with American Society of Anaesthesiologists physical status class I or II who were scheduled for elective surgery requiring anaesthesia and SLMA insertion.

Interventions: Leaving the blocker at the end of the pilot tube in situ (this blocker keeps the valve open and the balloon remains partially inflated but will deflate with pressure) or removing the blocker and actively deflating the cuff before SLMA insertion.

Main Outcome Measures: The primary outcome was the incidence of postoperative sore throat in the PACU. The secondary outcomes included sore throat severity (Prince Henry Hospital Pain Score), first-attempt success rate, ease of insertion, time to successful SLMA insertion, oropharyngeal leak pressure, grade of view on fibreoptic bronchoscopy (indicating the accuracy of SLMA positioning) and adverse events.

Results: The incidence of sore throat was 33/204 (16.2%) in the nonremoval group, and 65/204 (31.9%) in the removal group (P < 0.001). The first-attempt success rate was 174/204 (85.3%) in the nonremoval group and 150/204 (73.76%) in the removal group (P = 0.003; relative risk 1.160, 95% CI 1.049 to 1.282). The Kaplan--Meier curves showed that the insertion time in the nonremoval group was shorter (log-rank P = 0.01).

Conclusion: The new insertion technique, leaving the blocker attached to the end of the pilot balloon, resulted in a reduced incidence and severity of postoperative sore throat in the PACU, and an improved first-attempt success rate and the accuracy of SLMA positioning.

Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR1900023022.
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http://dx.doi.org/10.1097/EJA.0000000000001378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932751PMC
March 2021