Publications by authors named "Xiao Fan"

367 Publications

Acteoside, the Main Bioactive Compound in Flowers, Palliates Experimental Colitis in Mice by Regulating the Gut Microbiota.

J Agric Food Chem 2022 Jan 24. Epub 2022 Jan 24.

College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Key Laboratory for Agro-Products Nutritional Evaluation of Ministry of Agriculture and Rural Affairs, Key Laboratory of Agro-Products Postharvest Handling of Ministry of Agriculture and Rural Affairs, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang International Scientific and Technological Cooperation Base of Health Food Manufacturing and Quality Control, Zhejiang University, Hangzhou 310058, China.

The present study investigated the effects of flowers and acteoside on murine colitis and the underlying mechanisms. The flower extract (OFE) and acteoside were administrated to chemically induced colitic mice. The results showed that OFE or acteoside ameliorates intestinal inflammation, oxidative stress, and activation of nuclear factor-κB (NF-κB) in colitic mice. The dysbiosis of the gut microbiome in colitic mice was also partly restored by OFE or acteoside, which was characterized by the alteration of the gut microbiome structure and the enrichment of beneficial bacteria ( and ). Dextran sulfate sodium (DSS)-induced gut metabolome dysfunctions (e.g., sphingosine metabolism and amino acids metabolism) in colitic mice were also partly restored by OFE and acteoside. A fecal microbiota (FM) transplantation study suggested that, compared with the FM from the normal diet-dosed donor mice, the FM from the OFE- or acteoside-dosed donor mice significantly suppressed colitic symptoms.
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http://dx.doi.org/10.1021/acs.jafc.1c07583DOI Listing
January 2022

EOGT Correlated With Immune Infiltration: A Candidate Prognostic Biomarker for Hepatocellular Carcinoma.

Front Immunol 2021 5;12:780509. Epub 2022 Jan 5.

Department of Gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Background: A preliminary study by our group revealed that the deficiency of EGF domain-specific O-linked N-acetylglucosamine transferase (EOGT) impaired regulatory T-cell differentiation in autoimmune hepatitis. Nevertheless, the prognostic value of EOGT in advanced hepatocellular carcinoma (HCC) and its relationship with immune infiltration remain obscured.

Methods: Initially, EOGT expression was evaluated by Oncomine, TIMER, GEO, and UALCAN databases. Besides, the prognostic potential of EOGT expression was analyzed using GEPIA, Kaplan-Meier plotter, CPTAC, Cox regression, and nomogram in HCC samples. Furthermore, we investigated the association between EOGT expression and tumor mutation burden, DNA methylation, and immune infiltration in addition to its possible mechanism cBioPortal, TIMER, GEPIA, ESTIMATE, CIBERSORT, GSEA, STRING, and Cytoscape.

Results: The expression of EOGT in HCC was significantly higher than that in normal tissues. Additionally, elevated EOGT expression was correlated with advanced tumor staging and linked to poor overall survival and relapse-free survival, serving as a significant unfavorable prognostic indicator in HCC patients. Remarkably, our results revealed that high-EOGT expression subgroups with elevated or low mutations have worse clinical outcomes than the others. Regarding immune infiltration, immunofluorescent staining showed that immune cells in HCC were positive for EOGT. Besides, elevated EOGT expression was linked to exhausted T cells and immune suppressor cells in HCC samples. More importantly, the proportion of CD8 T cells was reduced in HCC samples with a high level of EOGT expression, but EOGT did not exhibit prognostic potential in HCC samples with increased CD8 T cells.

Conclusions: EOGT may hold great potential as a novel biomarker to distinguish prognosis and immune profiles of HCC patients.
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http://dx.doi.org/10.3389/fimmu.2021.780509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766744PMC
January 2022

Light-Harvesting Fluorescent Spherical Nucleic Acids Self-assembled from a DNA-Grafted Conjugated Polymer for Amplified Detection of Nucleic Acids.

Angew Chem Int Ed Engl 2022 Jan 21. Epub 2022 Jan 21.

Southern University of Science and Technology, Materials Science and Engineering, 1088 Xueyuan Blvd., Nanshan District, 518055, Shenzhen, CHINA.

The ultralow concentration of nucleic acids in complex biological samples desires fluorescence probes with high specificity and sensitivity. Herein, a new kind of spherical nucleic acids (SNAs) is developed by using fluorescent π-conjugated polymers (FCPs) as a light-harvesting antenna to enhance the signal transduction of nucleic acid detection. Specifically, amphiphilic DNA-grafted FCPs are synthesized and self-assemble into FCP-SNA structures. Tuning the hydrophobicity of the graft copolymer can adjust the size and light-harvesting capability of the FCP-SNAs. We observe that more efficient signal amplification occurs in larger FCP-SNAs, as more chromophores are involved, and the energy transfer can go beyond the Förster radius. Accordingly, the optimized FCP-SNA shows an antenna effect of up to 37-fold signal amplification and the limit of detection down to 1.7 pM in microRNA detection. Consequently, the FCP-SNA is applied to amplified in situ nucleic acid detecting and imaging at the single-cell level.
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http://dx.doi.org/10.1002/anie.202115812DOI Listing
January 2022

Correction to: Circular RNA hsa_circ_0000034 accelerates retinoblastoma advancement through the miR-361-3p/ADAM19 axis.

Mol Cell Biochem 2022 Jan 21. Epub 2022 Jan 21.

Department of Ophthalmology, The Fourth People's Hospital of Shenyang, No. 20 Huanghe South Street, Huanggu District, Shenyang, 110031, Liaoning, China.

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http://dx.doi.org/10.1007/s11010-021-04311-1DOI Listing
January 2022

The genetic architecture of pediatric cardiomyopathy.

Am J Hum Genet 2022 Jan 10. Epub 2022 Jan 10.

Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences at University at Buffalo and John R. Oishei Children's Hospital, Buffalo, NY 14203, USA.

To understand the genetic contribution to primary pediatric cardiomyopathy, we performed exome sequencing in a large cohort of 528 children with cardiomyopathy. Using clinical interpretation guidelines and targeting genes implicated in cardiomyopathy, we identified a genetic cause in 32% of affected individuals. Cardiomyopathy sub-phenotypes differed by ancestry, age at diagnosis, and family history. Infants < 1 year were less likely to have a molecular diagnosis (p < 0.001). Using a discovery set of 1,703 candidate genes and informatic tools, we identified rare and damaging variants in 56% of affected individuals. We see an excess burden of damaging variants in affected individuals as compared to two independent control sets, 1000 Genomes Project (p < 0.001) and SPARK parental controls (p < 1 × 10). Cardiomyopathy variant burden remained enriched when stratified by ancestry, variant type, and sub-phenotype, emphasizing the importance of understanding the contribution of these factors to genetic architecture. Enrichment in this discovery candidate gene set suggests multigenic mechanisms underlie sub-phenotype-specific causes and presentations of cardiomyopathy. These results identify important information about the genetic architecture of pediatric cardiomyopathy and support recommendations for clinical genetic testing in children while illustrating differences in genetic architecture by age, ancestry, and sub-phenotype and providing rationale for larger studies to investigate multigenic contributions.
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http://dx.doi.org/10.1016/j.ajhg.2021.12.006DOI Listing
January 2022

Response to Letter to the Editor.

J Ultrasound Med 2022 Jan 4. Epub 2022 Jan 4.

Department of Ultrasound, Lanzhou University Second Hospital, Lanzhou, Gansu, China.

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http://dx.doi.org/10.1002/jum.15928DOI Listing
January 2022

Genome-wide association studies for growth traits in broilers.

BMC Genom Data 2022 Jan 3;23(1). Epub 2022 Jan 3.

Key Laboratory of Chicken Genetics and Breeding, Ministry of Agriculture and Rural Affairs; Key Laboratory of Animal Genetics, Breeding and Reproduction, Education Department of Heilongjiang Province; College of Animal Science and Technology, Northeast Agricultural University, Harbin, 150030, P. R. China.

Background: The identification of markers and genes for growth traits may not only benefit for marker assist selection /genomic selection but also provide important information for understanding the genetic foundation of growth traits in broilers.

Results: In the current study, we estimated the genetic parameters of eight growth traits in broilers and carried out the genome-wide association studies for these growth traits. A total of 113 QTNs discovered by multiple methods together, and some genes, including ACTA1, IGF2BP1, TAPT1, LDB2, PRKCA, TGFBR2, GLI3, SLC16A7, INHBA, BAMBI, APCDD1, GPR39, and GATA4, were identified as important candidate genes for rapid growth in broilers.

Conclusions: The results of this study will provide important information for understanding the genetic foundation of growth traits in broilers.
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http://dx.doi.org/10.1186/s12863-021-01017-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725492PMC
January 2022

Diffuse leptomeningeal glioneuronal tumor without KIAA1549-BRAF fusion and 1p detection: a case report and review of literature.

Childs Nerv Syst 2022 Feb 3;38(2):279-285. Epub 2022 Jan 3.

Department of Radiology, The Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, China International Science and Technology Cooperation Base of Child development and Critical Disorders, Chongqing, China.

Background: Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare mixed neuronal-glial tumor of central nervous system. Chromosome microarray usually identifies co-deletion of the short arm of chromosome 1 and the long arm of chromosome 19 as well as fusion of the KIAA1549 and BRAF genes.

Methods: We describe a case of a 3-year-old boy with typical imaging and histopathological features, but without KIAA1549-BRAF fusion and 1p deletion. Additionally, a literature review is performed summarizing the clinical features, management, and prognosis of this rare entity.

Results: A 3-year-old boy presented with chronic headache and vomiting. On initial MRI scanning, diffuse thickening with enhancement of the cerebral and spinal leptomeninges could be detected after contrast injection. Multiple cystic lesions were found located on infratentorial leptomeninges, with progressive thickening of leptomeninges and increasing cysts on follow-up MRI after 9 months. Meningeal biopsy was carried out, showing that most of tumor cells were composed of oligodendroglioma-like cells. The tumor cells were immunopositive for GFAP, Olig-2, and synaptophysin but negative for IDH-1 and H3k27M. Molecular genetic testing did not detect KIAA1549-BRAF fusion, 1p deletion, or 1p/19q co-deletion. The patient was finally diagnosed as DLGNT after multidisciplinary team consultation.

Conclusions: Given that the clinical and pathological mechanism of DLGNTs remains unclear, our case gives supplement about the diversity of molecular genetic characteristics. Combination of clinical, neuroradiological, and histopathological data is particularly important for the diagnosis of DLGNTs, till now.
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http://dx.doi.org/10.1007/s00381-021-05426-yDOI Listing
February 2022

Dietary cholesterol oxidation products: Perspectives linking food processing and storage with health implications.

Compr Rev Food Sci Food Saf 2022 Jan 25;21(1):738-779. Epub 2021 Dec 25.

College of Biosystems Engineering and Food Science, National-Local Joint Engineering Laboratory of Intelligent Food Technology and Equipment, Key Laboratory for Agro-Products Nutritional Evaluation of Ministry of Agriculture and Rural Affairs, Key Laboratory of Agro-Products Postharvest Handling of Ministry of Agriculture and Rural Affairs, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang International Scientific and Technological Cooperation Base of Health Food Manufacturing and Quality Control, Zhejiang University, Hangzhou, China.

Dietary cholesterol oxidation products (COPs) are heterogeneous compounds formed during the processing and storage of cholesterol-rich foods, such as seafood, meat, eggs, and dairy products. With the increased intake of COPs-rich foods, the concern about health implications of dietary COPs is rising. Dietary COPs may exert deleterious effects on human health to induce several inflammatory diseases including atherosclerosis, neurodegenerative diseases, and inflammatory bowel diseases. Thus, knowledge regarding the effects of processing and storage conditions leading to formation of COPs is needed to reduce the levels of COPs in foods. Efficient methodologies to determine COPs in foods are also essential. More importantly, the biological roles of dietary COPs in human health and effects of phytochemicals on dietary COPs-induced diseases need to be established. This review summarizes the recent information on dietary COPs including their formation in foods during their processing and storage, analytical methods of determination of COPs, metabolic fate, implications for human health, and beneficial interventions by phytochemicals. The formation of COPs is largely dependent on the heating temperature, storage time, and food matrices. Alteration of food processing and storage conditions is one of the potent strategies to restrict hazardous dietary COPs from forming, including maintaining relatively low temperatures, shorter processing or storage time, and the appropriate addition of antioxidants. Once absorbed into the circulation, dietary COPs can contribute to the progression of several inflammatory diseases, where the absorbed dietary COPs may induce inflammation, apoptosis, and autophagy in cells in the target organs or tissues. Improved intake of phytochemicals may be an effective strategy to reduce the hazardous effects of dietary COPs.
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http://dx.doi.org/10.1111/1541-4337.12880DOI Listing
January 2022

B cell-activating factor and its targeted therapy in autoimmune diseases.

Cytokine Growth Factor Rev 2021 Dec 2. Epub 2021 Dec 2.

Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong; Chongqing International Institute for Immunology, Chongqing, China; Department of Rheumatology, Shenzhen Hospital, The University of Hong Kong, Shenzhen, China. Electronic address:

B cells play a pivotal role in the pathogenesis of autoimmune disease (AD) by the production of autoantibodies, secretion of cytokines and presentation of autoantigens. As a pro-survival factor mainly produced by myeloid cells, B cell-activating factor (BAFF) maintains B cell maturation and homeostasis at various B cell differentiation stages. Under autoimmune conditions, BAFF acts on autoreactive B cells that have escaped checkpoint apoptosis from negative selection. Numerous studies have shown increased levels of BAFF in patients with ADs and in mouse models with ADs wherein the production of autoantibodies is a prominent feature of immunopathology. Compelling evidence has indicated a key function of BAFF in driving autoreactive B cell response during autoimmune progression. Recent clinical studies have demonstrated BAFF as a therapeutic target in various ADs. Here, we review recent findings on BAFF expression and its effector mechanisms in autoimmune pathogenesis as well as newly developed therapeutic targeting of BAFF in the treatment of ADs.
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http://dx.doi.org/10.1016/j.cytogfr.2021.11.004DOI Listing
December 2021

Novel Perylene-3, 4, 9, 10-tetracarboxylic dianhydride modified Zr-MOFs/Graphene oxide membrane for dye wastewater treatment.

J Colloid Interface Sci 2022 Mar 23;610:671-686. Epub 2021 Nov 23.

School of Materials Science and Engineering, State Key Laboratory of Separation Membranes and Membrane Processes, Tiangong University, Tianjin 300387, PR China.

A new type of composite membrane was prepared through the vacuum filtration self-assembly, in which, graphene oxide (GO) was the basic material, and the horizontal insertion material is product of perylene-3, 4, 9, 10-tetracarboxylic dianhydride (PTCDA) and UiO-66-NH (PTCDA-UiO-66-NH). The leading role of Π-Π conjugate, auxiliary effect of hydrogen bonding during membrane preparation have been confirmed through Fourier transform infrared spectroscopy (FTIR), UV-visible spectrophotometer, Raman spectroscopy, and X-ray diffraction (XRD). The prepared [email protected] membrane had new nodular structure compared to GO membrane by scanning electron microscopy (SEM) and atomic force microscopy (AFM), which promoted the water transport. In addition, the insertion of PTCDA-UiO-66-NH narrowed the actual filtration spacing between GO sheets, and PTCDA-UiO-66-NH could also adsorbed dye laterally. Experiments showed that the permeance of [email protected] membrane was 1.7 times of GO membrane, and the removal of methyl blue, congo red, crystal violet and disperse black 9 was close to 100%. Under extreme pH, high salt concentration and multiple recycling, its separation ability was still excellent. The [email protected] membrane constituted a unique synergistic structure of vertical-screening and horizontal-adsorption, which successfully overcame the trade-off effect and obtained excellent stability of structure and performance. Therefore, [email protected] membrane had great potential in practical applications.
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http://dx.doi.org/10.1016/j.jcis.2021.11.113DOI Listing
March 2022

Meteorin-β/Meteorin like/IL-41 attenuates airway inflammation in house dust mite-induced allergic asthma.

Cell Mol Immunol 2021 Nov 30. Epub 2021 Nov 30.

Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China.

We sought to examine the regulatory effect of Meteorin-β (Metrnβ)/Meteorin like (Metrnl)/IL-41 on lung inflammation in allergic asthma. We found that Metrnβ was elevated significantly in asthmatic patients and in mice with allergic asthma induced by house dust mite (HDM) extract. Upon exposure to HDM, Metrnβ was secreted predominantly by airway epithelial cells and inflammatory cells, including macrophages and eosinophils. The increased Metrnβ effectively blocked the development of airway hyperreactivity (AHR) and decreased inflammatory cell airway infiltration and type 2 cytokine production, which was associated with downregulated DC-mediated adaptive immune responses. Moreover, Metrnβ impaired the maturation and function of bone marrow-derived dendritic cells in vitro. Asthmatic mice adoptively transferred with dendritic cells isolated from Metrnβ-treated allergic mice displayed decreased AHR, airway inflammation, and lung injury. Metrnβ also displayed anti-inflammatory properties in immunodeficient SCID mice with allergic asthma and in in vitro 3D ALI airway models. Moreover, blockade of Metrnβ by anti-Metrnβ antibody treatment promoted the development of allergic asthma. These results revealed the unappreciated protective roles of Metrnβ in alleviating DC-mediated Th2 inflammation in allergic asthma, providing the novel treatment strategy of therapeutic targeting of Metrnβ in allergic asthma.
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http://dx.doi.org/10.1038/s41423-021-00803-8DOI Listing
November 2021

Contrast-Enhanced Ultrasound for Precise Sentinel Lymph Node Biopsy in Women with Early Breast Cancer: A Preliminary Study.

Diagnostics (Basel) 2021 Nov 13;11(11). Epub 2021 Nov 13.

Ultrasound Medicine Center, Lanzhou University Second Hospital, Lanzhou 730030, China.

Background: Sentinel lymph node biopsy (SLNB), as a common method for axillary staging of early breast cancer, has gradually attracted people's attention to the false-negative rate and postoperative complications. The aim of the study is to investigate the clinical value of preoperative contrast-enhanced ultrasound (CEUS) for intraoperative SLNB in early breast cancer patients.

Methods: A total of 201 patients scheduled for SLNB from September 2018 to April 2021 were collected consecutively. Preoperative CEUS was used to identify sentinel lymph nodes (SLN) and lymphatic drainage in breast cancer patients.

Results: The SLN identification rate of CEUS was 93.0% (187/201) and four lymphatic drainage patterns were found: single LC to single SLN (70.0%), multiple LCs to single SLN (8.0%), single LC to multiple SLNs (10.2%), and multiple LCs to multiple SLNs (11.8%). The Sen, Spe, PPV, NPV, AUC of CEUS, US and CEUS + US in diagnosis of SLNs were 82.7%, 80.4%, 73.8%, 87.4%, 0.815; 70.7%, 77.7%, 68.0%, 79.8%, 0.742; and 86.7%, 77.7%, 72.2%, 89.7%, 0.822, respectively. There was no statistically significant difference between the diagnostic performance of CEUS and CEUS + US ( = 0.630).

Conclusions: CEUS can be used to preoperatively assess the lymphatic drainage patterns and the status of the SLNs in early breast cancer to assist precision intraoperative SLNB.
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http://dx.doi.org/10.3390/diagnostics11112104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624576PMC
November 2021

Deep learning-based 3Ddose reconstruction with an electronic portal imaging device for magnetic resonance-linear accelerators: a proof of concept study.

Phys Med Biol 2021 Dec 2;66(23). Epub 2021 Dec 2.

School of Biomedical Engineering, Southern Medical University, Guangzhou, People's Republic of China.

To develop a novel deep learning-based 3Ddose reconstruction framework with an electronic portal imaging device (EPID) for magnetic resonance-linear accelerators (MR-LINACs).The proposed method directly back-projected 2D portal dose into 3D patient coarse dose, which bypassed the complicated patient-to-EPID scatter estimation step used in conventional methods. A pre-trained convolutional neural network (CNN) was then employed to map the coarse dose to the final accurate dose. The electron return effect caused by the magnetic field was captured with the CNN model. Patient dose and portal dose datasets were synchronously generated with Monte Carlo simulation for 96 patients (78 cases for training and validation and 18 cases for testing) treated with fixed-beam intensity-modulated radiotherapy in four different tumor sites, including the brain, nasopharynx, lung, and rectum. Beam angles from the training dataset were further rotated 2-3 times, and doses were recalculated to augment the datasets.The comparison between reconstructed doses and MC ground truth doses showed mean absolute errors <0.88% for all tumor sites. The averaged 3D-passing rates (3%, 2 mm) were 97.42%±2.66% (brain), 98.53%±0.95% (nasopharynx), 99.41%±0.46% (lung), and 98.63%±1.01% (rectum). The dose volume histograms and indices also showed good consistency. The average dose reconstruction time, including back projection and CNN dose mapping, was less than 3 s for each individual beam.The proposed method can be potentially used for accurate and fast 3D dosimetric verification for online adaptive radiotherapy using MR-LINACs.
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http://dx.doi.org/10.1088/1361-6560/ac3b66DOI Listing
December 2021

Deubiquitinase ZRANB1 drives hepatocellular carcinoma progression through SP1-LOXL2 axis.

Am J Cancer Res 2021 15;11(10):4807-4825. Epub 2021 Oct 15.

Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University Nanchang, Jiangxi, China.

Deubiquitinase (DUB) zinc finger RANBP2-type containing 1 (ZRANB1) has been reported to have a close relationship with cancers. However, its underlying role and molecular mechanisms in hepatocellular carcinoma (HCC) remain elusive. In this study, we demonstrated that ZRANB1 was highly expressed in HCC tissues. Additionally, ZRANB1 overexpression was correlated with poorer survival and ZRANB1 could be an independent predictor of poor prognosis for HCC patients. Through gain- and loss-of-function assays, we examined the oncogenic role of ZRANB1 in regulating HCC cell growth and metastasis and . To identify the downstream targets of ZRANB1 in regulating HCC tumorigenesis, we performed RNA-seq and demonstrated that Lysyl oxidase-like 2 (LOXL2) was the most significantly downregulated gene after ZRANB1 knockdown. Furthermore, the scatter plots indicated a significant positive correlation between ZRANB1 and LOXL2 expression in clinical HCC specimens. We also demonstrated that ZRANB1 knockdown downregulated the expression of LOXL2 and suppressed HCC growth and metastasis and . The effects of ZRANB1 knockdown were reversed by LOXL2 overexpression. More importantly, ZRANB1 regulated LOXL2 through specificity protein 1 (SP1) and SP1 overexpression rescued the suppression of HCC growth and metastasis induced by ZRANB1 knockdown. Mechanistically, ZRANB1 bound with SP1 directly and stabilized the SP1 protein by deubiquitinating it. The expression patterns of ZRANB1, SP1 and LOXL2 were evaluated in HCC patients. In summary, our research highlights a novel role of ZRANB1 in the tumorigenesis of HCC and suggests a new candidate prognostic biomarker for HCC treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569347PMC
October 2021

Noncognitive species-typical and home-cage behavioral alterations in conditional presenilin 1/presenilin 2 double knockout mice.

Behav Brain Res 2022 Feb 7;418:113652. Epub 2021 Nov 7.

Key Laboratory of Brain Functional Genomics, Ministry of Education, School of Life Sciences, East China Normal University, Shanghai 200062, China. Electronic address:

Impairments in activities of daily living (ADL) are common clinical symptoms of human Alzheimer's disease (AD). Describing the ADL in AD animal models might provide more insights into the mechanism/treatment of the disease. Here, we demonstrated that the forebrain presenilin 1(Psen1)/presenilin 2 (Psen2) conditional double knockout (DKO) mice exhibited deficits in nest building, marble burying and food burrowing starting at 3 months old and worsening at later ages. At 4 months of age, spontaneous activities in the home cage were also impaired in DKO mice, including physically demanding activities, habituation-like behaviors, and nourishment behaviors during the first two hours in the dark phase. These results indicated that loss of function of Psen1 and Psen2 in mice impaired a series of noncognitive behaviors in the early phase of neurodegeneration. This observation suggests that DKO mice are an ideal model for further mechanistic studies of Psen1 and Psen2 functions in regulating noncognitive behaviors.
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http://dx.doi.org/10.1016/j.bbr.2021.113652DOI Listing
February 2022

Single Dose of SHR-1222, a Sclerostin Monoclonal Antibody, in Healthy Men and Postmenopausal Women With Low Bone Mass: A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation, Phase I Study.

Front Pharmacol 2021 20;12:770073. Epub 2021 Oct 20.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

SHR-1222 is a humanized monoclonal antibody targeting sclerostin and has the potential to promote bone formation and reduce bone resorption. This study was aimed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of SHR-1222 in healthy men and postmenopausal women with low bone mass (BMD). It was a randomized, double-blind, placebo-controlled, dose-escalation, phase I study. Subjects received SHR-1222 at 50, 100, 200, 300, and 400 mg sequentially or matching placebo subcutaneously. Totally, 50 subjects with low BMD were enrolled and randomly assigned; 10 received placebo and 40 received SHR-1222 (50 mg, n = 4; 100, 200, 300, or 400 mg, n = 9). The most common adverse events that occurred at least 10% higher in subjects with SHR-1222 treatment than those with placebo were decreased blood calcium, blood urine present, increased blood cholesterol, electrocardiogram T wave abnormal, urinary tract infection, increased blood pressure diastolic, and positive bacterial test. All the above adverse events were mild in severity and well resolved except one of increased blood cholesterol in a subject lost to follow-up. The serum SHR-1222 concentration increased in a dose-dependent manner. Administration of SHR-1222 upregulated the bone-formation markers N-terminal propeptide of type 1 procollagen, osteocalcin, and bone-specific alkaline phosphatase, while downregulated the bone-resorption marker β-C-telopeptide. The BMD at the lumbar spine notably rose after a single dose of SHR-1222. The largest increase occurred in the 400 mg cohort (3.8, 6.7, and 6.1% on day 29, 57, and 85, respectively; compared with 1.4, 0.8, and 1.0% in the placebo group). Although 10.0% of subjects receiving SHR-1222 tested positive for anti-SHR-1222 antibodies, no obvious effects of antibody formation were found on pharmacokinetics. Overall, SHR-1222 was well tolerated at doses from 50 to 400 mg and is a promising new remedy for osteoporosis. http://www.clinicaltrials.gov, NCT03870100.
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http://dx.doi.org/10.3389/fphar.2021.770073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564351PMC
October 2021

Effect of the Ethylene Vinyl Acetate Copolymer on the Induction of Cyclopentane Hydrate in a Water-in-Waxy Oil Emulsion System.

Langmuir 2021 Nov 4;37(45):13225-13234. Epub 2021 Nov 4.

Beijing Key Laboratory of Urban Oil and Gas Distribution Technology, State Key Laboratory of Natural Gas Hydrates, MOE Key Laboratory of Petroleum Engineering, China University of Petroleum-Beijing, No.18 Fuxue Road, Changping, Beijing 102249, PR China.

In this paper, the effect of the ethylene vinyl acetate (EVA) copolymer, commonly used in improving rheological behavior of waxy oil, is introduced to investigate its effect on the formation of cyclopentane hydrate in a water-in-waxy oil emulsion system. The wax content studied shows a negative effect on the formation of hydrate by elongating its induction time. Besides, the EVA copolymer is found to elongate the induction time of cyclopentane hydrate through the cocrystallization effect with wax molecules adjacent to the oil-water interface.
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http://dx.doi.org/10.1021/acs.langmuir.1c01734DOI Listing
November 2021

Polymorphisms in BMPRIB gene affect litter size in Chinese indigenous sheep breed.

Anim Biotechnol 2021 Sep 27:1-8. Epub 2021 Sep 27.

College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China.

The BMPRIB gene belongs to the TGF-β superfamily and is considered to be a regulator of sheep reproductive performance. Single nucleotide polymorphisms (SNPs) of BMPRIB gene in the Small Tail Han, Hu, Mongolian, Oula, Gansu Alpine Fine-wool, Dorper and Australian White sheep were detected by Sanger sequencing. Five SNPs (rs427897187 G > A, rs418841713 A > G, rs159952533 T > C, rs429416173 C > A and rs403555643 A > G) of BMPRIB gene were identified. For rs427897187 G > A, further analysis revealed that genotype GG and GA had 0.26 ( < 0.05) and 0.33 ( < 0.05) litter size less than those with genotype AA in Oula sheep. For rs403555643 A > G, further analysis revealed that genotype GG and AG had 0.65 ( < 0.05) and 0.38 ( < 0.05) litter size more than those with genotype AA in Oula sheep, and genotype GG had 0.56 ( < 0.05) litter size more than those with genotype AA in Mongolian sheep. The results showed that rs427897187 G > A and rs403555643 A > G are potential molecular markers wich could improve litter size of Chinese indigenous sheep and be used in Chinese indigenous sheep breeding.
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http://dx.doi.org/10.1080/10495398.2021.1980400DOI Listing
September 2021

Decreased Glucagon-Like Peptide-1 Is Associated With Calcific Aortic Valve Disease: GLP-1 Suppresses the Calcification of Aortic Valve Interstitial Cells.

Front Cardiovasc Med 2021 26;8:709741. Epub 2021 Aug 26.

Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

This study explores the concentration and role of glucagon-like peptide-1 (GLP-1) in calcific aortic valve disease (CAVD). Calcific aortic valve disease is a chronic disease presenting with aortic valve degeneration and mineralization. We hypothesized that the level of GLP-1 is associated with CAVD and that it participates in the calcification of aortic valve interstitial cells (AVICs). We compared the concentration of GLP-1 between 11 calcific and 12 normal aortic valve tissues by immunohistochemical (IHC) analysis. ELISA was used to measure GLP-1 in serum of the Control ( = 197) and CAVD groups ( = 200). The effect of GLP-1 on the calcification of AVICs and the regulation of calcific gene expression were also characterized. The GLP-1 concentration in the calcific aortic valves was 39% less than that in the control non-calcified aortic valves. Its concentration in serum was 19.3% lower in CAVD patients. Multivariable regression analysis demonstrated that GLP-1 level was independently associated with CAVD risk. , GLP-1 antagonized AVIC calcification in a dose- and time-dependent manner and it down-regulated RUNX2, MSX2, BMP2, and BMP4 expression but up-regulated SOX9 expression. A reduction in GLP-1 was associated with CAVD, and GLP-1 participated in the mineralization of AVICs by regulating specific calcific genes. GLP-1 warrants consideration as a novel treatment target for CAVD.
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http://dx.doi.org/10.3389/fcvm.2021.709741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428521PMC
August 2021

Non-cancer-related pathogenic germline variants and expression consequences in ten-thousand cancer genomes.

Genome Med 2021 09 9;13(1):147. Epub 2021 Sep 9.

Department of Genetics and Genomic Sciences, Center for Transformative Disease Modeling, Tisch Cancer Institute, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.

Background: DNA sequencing is increasingly incorporated into the routine care of cancer patients, many of whom also carry inherited, moderate/high-penetrance variants associated with other diseases. Yet, the prevalence and consequence of such variants remain unclear.

Methods: We analyzed the germline genomes of 10,389 adult cancer cases in the TCGA cohort, identifying pathogenic/likely pathogenic variants in autosomal-dominant genes, autosomal-recessive genes, and 59 medically actionable genes curated by the American College of Molecular Genetics (i.e., the ACMG 59 genes). We also analyzed variant- and gene-level expression consequences in carriers.

Results: The affected genes exhibited varying pan-ancestry and population-specific patterns, and overall, the European population showed the highest frequency of pathogenic/likely pathogenic variants. We further identified genes showing expression consequence supporting variant functionality, including altered gene expression, allelic specific expression, and mis-splicing determined by a massively parallel splicing assay.

Conclusions: Our results demonstrate that expression-altering variants are found in a substantial fraction of cases and illustrate the yield of genomic risk assessments for a wide range of diseases across diverse populations.
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http://dx.doi.org/10.1186/s13073-021-00964-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431938PMC
September 2021

Hydrogen sulphide attenuates neuronal apoptosis of substantia nigra by re-establishing autophagic flux via promoting leptin signalling in a 6-hydroxydopamine rat model of Parkinson's disease.

Clin Exp Pharmacol Physiol 2022 01 22;49(1):122-133. Epub 2021 Sep 22.

The First Affiliated Hospital, Institute of Neurology, Hengyang Medical School, University of South China, Hengyang, Hunan, China.

Previous studies reveal that hydrogen sulphide (H S) exerts neuroprotection against neurotoxin-induced Parkinson's disease (PD), but the underlying mechanism remains elusive. The present study was aimed to investigate whether H S inhibits neuronal apoptosis of substantia nigra with the involvement of autophagy via promoting leptin signalling in 6-hydroxydopamine (6-OHDA)-induced PD rats. In this study, neuronal apoptosis was analysed by TUNEL staining, the activity of caspase-3 was measured by Caspase-3 fluorometric assay kit, the expressions of Bax, Bcl-2, Beclin-1, LC3II, P62 and leptin were determined by Western blot analysis, and the numbers of autophagosomes and autolysosomes were assessed by transmission electron microscopy. Results showed that NaHS, a donor of exogenous H S, mitigates 6-OHDA-induced the increases in the numbers of TUNEL-positive cells, the activity of caspase-3 and the expression of Bax, and attenuates 6-OHDA-induced a decrease in the expression of Bcl-2 in substantia nigra of rats. In addition, 6-OHDA enhanced the expressions of Beclin-1, LC3-II and P62, increased the number of autophagosomes, and decreased the number of autolysosomes in the substantia nigra, which were also blocked by administration of NaHS. Furthermore, NaHS reversed 6-OHDA-induced the down-regulation of leptin expression in the substantia nigra, and treatment with leptin-OBR, a blocking antibody of leptin receptor, attenuated the inhibition of NaHS on neuronal apoptosis and the improvement of NaHS on the blocked autophagic flux in substantia nigra of 6-OHDA-treated rats. Taken together, these results demonstrated that H S attenuates neuronal apoptosis of substantia nigra depending on restoring impaired autophagic flux through up-regulating leptin signalling in PD.
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http://dx.doi.org/10.1111/1440-1681.13587DOI Listing
January 2022

Changes in Conjunctival Microbiota Associated With HIV Infection and Antiretroviral Therapy.

Invest Ophthalmol Vis Sci 2021 09;62(12)

Institute of Ophthalmology, School of Medicine, Jinan University, Guangzhou, China.

Purpose: HIV infection is associated with a variety of ocular surface diseases. Understanding the difference of the ocular microbiota between HIV-infected and healthy individuals as well as the influence of antiretroviral therapy will help to investigate the pathogenesis of these conditions.

Methods: A cross-sectional study was conducted on subjects including HIV-negative individuals, untreated HIV-infected individuals, and HIV-infected individuals with antiretroviral therapy. Conjunctival microbiota was assessed by bacterial 16S rRNA sequencing of the samples obtained from the conjunctival swab.

Results: The microbial richness in ocular surface was similar in HIV-negative, untreated HIV-positive, and highly active antiretroviral therapy (HAART) subjects. The bacterial compositions were similar in the two HIV infection groups but were significantly different from the HIV-negative group. HAART changed the beta diversity of bacterial community as determined by Shannon index. CD4+ T cell count had no significant influence on the diversity of ocular microbiota in HIV-infected individuals.

Conclusions: The data revealed the compositional and structural difference in conjunctival microbial community in subjects with and without HIV infection, indicating that HIV infection or its treatment, may contribute to ocular surface dysbiosis.
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http://dx.doi.org/10.1167/iovs.62.12.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419876PMC
September 2021

1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study.

Lancet 2021 08;398(10302):747-758

Department of Pulmonary and Critical Care Medicine, National Center for Respiratory Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China; Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China; Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, China. Electronic address:

Background: The full range of long-term health consequences of COVID-19 in patients who are discharged from hospital is largely unclear. The aim of our study was to comprehensively compare consequences between 6 months and 12 months after symptom onset among hospital survivors with COVID-19.

Methods: We undertook an ambidirectional cohort study of COVID-19 survivors who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. At 6-month and 12-month follow-up visit, survivors were interviewed with questionnaires on symptoms and health-related quality of life (HRQoL), and received a physical examination, a 6-min walking test, and laboratory tests. They were required to report their health-care use after discharge and work status at the 12-month visit. Survivors who had completed pulmonary function tests or had lung radiographic abnormality at 6 months were given the corresponding tests at 12 months. Non-COVID-19 participants (controls) matched for age, sex, and comorbidities were interviewed and completed questionnaires to assess prevalent symptoms and HRQoL. The primary outcomes were symptoms, modified British Medical Research Council (mMRC) score, HRQoL, and distance walked in 6 min (6MWD). Multivariable adjusted logistic regression models were used to evaluate the risk factors of 12-month outcomes.

Findings: 1276 COVID-19 survivors completed both visits. The median age of patients was 59·0 years (IQR 49·0-67·0) and 681 (53%) were men. The median follow-up time was 185·0 days (IQR 175·0-198·0) for the 6-month visit and 349·0 days (337·0-361·0) for the 12-month visit after symptom onset. The proportion of patients with at least one sequelae symptom decreased from 68% (831/1227) at 6 months to 49% (620/1272) at 12 months (p<0·0001). The proportion of patients with dyspnoea, characterised by mMRC score of 1 or more, slightly increased from 26% (313/1185) at 6-month visit to 30% (380/1271) at 12-month visit (p=0·014). Additionally, more patients had anxiety or depression at 12-month visit (26% [331/1271] at 12-month visit vs 23% [274/1187] at 6-month visit; p=0·015). No significant difference on 6MWD was observed between 6 months and 12 months. 88% (422/479) of patients who were employed before COVID-19 had returned to their original work at 12 months. Compared with men, women had an odds ratio of 1·43 (95% CI 1·04-1·96) for fatigue or muscle weakness, 2·00 (1·48-2·69) for anxiety or depression, and 2·97 (1·50-5·88) for diffusion impairment. Matched COVID-19 survivors at 12 months had more problems with mobility, pain or discomfort, and anxiety or depression, and had more prevalent symptoms than did controls.

Interpretation: Most COVID-19 survivors had a good physical and functional recovery during 1-year follow-up, and had returned to their original work and life. The health status in our cohort of COVID-19 survivors at 12 months was still lower than that in the control population.

Funding: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, the China Evergrande Group, Jack Ma Foundation, Sino Biopharmaceutical, Ping An Insurance (Group), and New Sunshine Charity Foundation.
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http://dx.doi.org/10.1016/S0140-6736(21)01755-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389999PMC
August 2021

ZIP4 promotes non-small cell lung cancer metastasis by activating snail-N-cadherin signaling axis.

Cancer Lett 2021 Aug 24;521:71-81. Epub 2021 Aug 24.

Department of Medicine, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Surgery, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Electronic address:

Non-small cell lung cancer (NSCLC) is one of the most critical health problems worldwide, with high incidence and poor survival rate. A zinc importer ZIP4 has been implicated in the process of tumor growth and metastasis of many cancers. However, its exact role and the underlying mechanism in NSCLC remains to be elucidated. In the present study, we found that human ZIP4 was substantially overexpressed in NSCLC tissues and was correlated with poor overall survival (OS) and progression-free survival (PFS). Overexpression of ZIP4 promoted cell migration, invasion and metastasis both in vitro and in a mouse lung metastasis model. Silencing of ZIP4 attenuated migration, invasion and metastasis. Mechanistically, overexpression of ZIP4 increased the expression of Snail, Slug and N-cadherin while genetic inactivation of ZIP4 downregulated the expression of above-mentioned genes. Further analysis showed that transcriptional factor Snail which modulates N-cadherin was involved in the process of ZIP4-mediated NSCLC migration and invasion. We also demonstrated that ZIP4 positively correlates with the levels of Snail, Slug and N-cadherin in mice lung metastasis tumors. Together, these results suggest that ZIP4 acts as an important regulator of Snail-N-cadherin signaling axis in promoting NSCLC progression and may serve as a novel predictive marker and therapeutic target in NSCLC.
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http://dx.doi.org/10.1016/j.canlet.2021.08.025DOI Listing
August 2021

Value of Echogenic Foci in Diagnosing Papillary Thyroid Carcinoma and Predicting Aggressive Biological Behavior.

J Ultrasound Med 2021 Aug 20. Epub 2021 Aug 20.

Department of Ultrasound, Lanzhou University Second Hospital, Lanzhou, Gansu, China.

Objectives: To assess the diagnostic value of echogenic foci in papillary thyroid carcinoma (PTC) and the relationship between echogenic foci and aggressiveness of PTC.

Methods: From January 2018 to January 2021, a total of 950 patients diagnosed with thyroid nodules (n = 1113) in our hospital were retrospectively analyzed. Among the 1113 nodules, single PTC in 527 patients confirmed by surgery was studied for their aggressive biological behavior. The patterns of echogenic foci were classified as: no echogenic foci, sparse punctate echogenic foci, focal punctate echogenic foci, diffuse punctate echogenic foci, petal-like punctate echogenic foci, comet-tail artifacts, coarse echogenic foci, peripheral rim (eggshell echogenic foci), and mixed echogenic foci. The clinical and ultrasonographic characteristics were also analyzed. A univariate analysis was performed, and binary logistic regression was performed to screen independent risk factors.

Results: For the differential diagnosis of PTC, age < 50 years, size <1.1 cm, hypoechoic or very hypoechoic, aspect ratio > 1, irregular shape, types II (punctate echogenic foci) and VI (mixed echogenic foci) were independent risk factors. For the aggressive biological behavior of PTC, male sex, age<42 years, size <1.0 cm, types IIb (focal punctate echogenic foci), IIc (diffuse punctate echogenic foci), and VI (mixed echogenic foci) were independent risk factors for predicting cervical lymph node metastasis of PTC.

Conclusion: Echogenic foci are useful in diagnosing PTC and predicting aggressiveness of PTC, which contribute to screening invasive PTC and avoiding overdiagnosis and overtreatment.
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http://dx.doi.org/10.1002/jum.15815DOI Listing
August 2021

Penetrance of Breast Cancer Susceptibility Genes From the eMERGE III Network.

JNCI Cancer Spectr 2021 Aug 8;5(4):pkab044. Epub 2021 May 8.

Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.

Background: Unbiased estimates of penetrance are challenging but critically important to make informed choices about strategies for risk management through increased surveillance and risk-reducing interventions.

Methods: We studied the penetrance and clinical outcomes of 7 breast cancer susceptibility genes (, , , , , , and ) in almost 13 458 participants unselected for personal or family history of breast cancer. We identified 242 female participants with pathogenic or likely pathogenic variants in 1 of the 7 genes for penetrance analyses, and 147 women did not previously know their genetic results.

Results: Out of the 147 women, 32 women were diagnosed with breast cancer at an average age of 52.8 years. Estimated penetrance by age 60 years ranged from 17.8% to 43.8%, depending on the gene. In clinical-impact analysis, 42.3% (95% confidence interval = 31.3% to 53.3%) of women had taken actions related to their genetic results, and 2 new breast cancer cases were identified within the first 12 months after genetic results disclosure.

Conclusions: Our study provides population-based penetrance estimates for the understudied genes , , and and highlights the importance of using unselected populations for penetrance studies. It also demonstrates the potential clinical impact of genetic testing to improve health care through early diagnosis and preventative screening.
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http://dx.doi.org/10.1093/jncics/pkab044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346699PMC
August 2021

[Effects of miR-335-5p targeting G6PD on proliferation and apoptosis of colon cancer cells].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2021 Jul;37(4):402-406

Department ofLaboratory, Sanya People's Hospital, Sanya 572000, China.

To investigate the effects of miR-335-5p targeting glucose-6-phosphate dehydrogenase (G6PD) on the proliferation and apoptosis of colon cancer cells. Normal colon cell group, blank control group, NC group and miRNA-335-5p mimic group were set up. Colonic epithelial cells (IEC) and human colon cancer cells SW480 were cultured in vitro, and the cells in the NC group and miRNA-335-5p mimic group cells were transfected. RT-qPCR was used to detect the expression levels of miR-335-5p and G6PD mRNA in each group of cells. The targeting effect of miR-335-5p on G6PD was verified by Double Luciferase Report experiment. MTT assay was used to detect cell proliferation. Flow cytometry was used to detect the apoptosis rate. The expressions of G6PD, Bax, Bcl-2 and caspase-3 were detected by Western blot. Compared with normal colon cells, the relative expression levels of miR-335-5p in SW480 cells of colon cancer in the blank control group and NC group were decreased, and the relative expression level of G6PD mRNA was increased (<0.05); compared with the blank control group and NC group, the expression level of miR-335-5p in miR-335-5p mimic group was increased significantly, and the expression of G6PD mRNA was decreased significantly (<0.05). Compared with the blank control group and NC group, the proliferative activity of colon cancer SW480 cells in miR-335-5p mimic group was decreased significantly, and the apoptosis rate was increased significantly (<0.05). The relative activity of luciferase in miR-335-5p mimic + WT-G6PD 3 '- UTR group was lower than that in miR-335-5p NC + WT-G6PD 3' - UTR group (<0.05). Compared with the blank control group, the relative expression levels of G6PD and bcl-2 protein in miR-335-5p mimic group were decreased significantly, and the expression levels of Bax and caspase-3 protein were increased significantly (<0.05). MiR-335-5p may inhibit the proliferation and promote apoptosis of colon cancer cells by targeting G6PD.
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http://dx.doi.org/10.12047/j.cjap.6090.2021.041DOI Listing
July 2021

[Changes of FLI-1 protein expression in mice with pulmonary endothelial barrier dysfunction following acute lung injury induced by lipopolysaccharide].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2021 Jul;37(4):393-396

Institute of Hypoxia Medicine, Wenzhou Medical University, Wenzhou 325035, China.

To observe changes of Friend leukemia virus integration 1 (FLI-1) protein expression of pulmonary tissue in mice with pulmonary endothelial barrier dysfunction following acute lung injury (ALI) induced by lipopolysaccharide (LPS). The mouse model of ALI was established by injection of LPS (7.5 mg/kg, i.p. ). At 0 h, 12 h, 24 h and 48 h after LPS injection, pulmonary microvascular endothelial permeability and lung wet/dry weight ratio (W/D) were assessed. The contents of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF) were detected by ELISA method. The protein levels of FLI-1 and Src protein tyrosine kinase (SRC) were analyzed by Western blotting. ①Pulmonary microvascular endothelial permeability at 12 h and 24 h were significantly higher than those of 0 h by 74.3% and 162.4%, respectively, while that of 48 h was lower than that of 24 h by 27.0% (<0.05). The W/D at 12 h and 24 h were significantly higher than those of 0 h by 50.1% and 122.9%, respectively, while that of 48 h was lower than that of 24 h by 10.7% (<0.05). ②The contents of IL-6 and TNF-α in BALF at 12 h and 24 h were significantly higher than those of 0 h, while those of 48 h were significantly lower than those of 24 h by 28.3% and 21.6% (<0.05), respectively. ③The protein level of FLI-1 in lung at 12 h and 24 h were down-regulated than those of 0 h by 20.4% and 56.9%, respectively, while that of 48 h was up-regulated than that of 24 h by 18.2% (<0.05). The protein level of SRC in lung at 12 h and 24 h were up-regulated than those of 0 h by 76.8% and 176.7%, respectively, while that of 48 h was down-regulated than that of 24 h by 33.4% (<0.05).④Same as the protein level of FLI-1 with the protein level of SRC in lung, pulmonary microvascular endothelial permeability was significantly negative correlated with the protein level of FLI-1 in lung, while it was significantly positive correlated with the protein level of SRC (<0.01). FLI-1 participates in the pathological proceeding of pulmonary endothelial barrier dysfunction following ALI induced by LPS.
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http://dx.doi.org/10.12047/j.cjap.6080.2021.040DOI Listing
July 2021
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