Publications by authors named "Hui Ding"

632 Publications

Prevalence and Antifungal Susceptibility of Species Complex in Eastern China: A 15-Year Retrospective Study by ECIFIG.

Front Microbiol 2021 4;12:644000. Epub 2021 Mar 4.

Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

complex is one of the most common non- species that cause candidemia, especially invasive candidiasis. The purpose of this study was to evaluate the antifungal susceptibilities of both colonized and invasive clinical complex isolates to 10 drugs: amphotericin (AMB), anidulafungin (AFG), caspofungin (CAS), micafungin (MFG), fluconazole (FLZ), voriconazole (VRZ), itraconazole (ITZ), posaconazole (POZ), 5-flucytosine (FCY), and isaconazole (ISA). In total, 884 species complex isolates were gathered between January 2005 and December 2020. , , and accounted for 86.3, 8.1, and 5.5% of the cryptic species, respectively. The resistance/non-wild-type rate of bloodstream to the drugs was 3.5%, of to AFG and CAS was 7.7%, and of to FLZ and VRZ was 15% and to CAS, MFG, and POZ was 5%. The geometric mean (GM) minimum inhibitory concentrations (MICs) of non-bloodstream for CAS (0.555 mg/L), MFG (0.853 mg/L), FLZ (0.816 mg/L), VRZ (0.017 mg/L), ITZ (0.076 mg/L), and POZ (0.042 mg/L) were significantly higher than those of bloodstream , for which the GM MICs were 0.464, 0.745, 0.704, 0.015, 0.061, and 0.033 mg/L, respectively ( < 0.05). The MIC distribution of the bloodstream strains collected from 2019 to 2020 for VRZ, POZ, and ITZ were 0.018, 0.040, and 0.073 mg/L, significantly higher than those from 2005 to 2018, which were 0.013, 0.028, and 0.052 mg/L ( < 0.05). Additionally, MIC distributions of with FLZ and the distributions of with ITZ and POZ might be higher than those in Clinical and Laboratory Standards Institute studies. Furthermore, a total of 143 complex isolates showed great susceptibility to ISA. Overall, antifungal treatment of the non-bloodstream complex isolates should be managed and improved. The clinicians are suggested to pay more attention on azoles usage for the complex isolates. In addition, establishing the epidemiological cutoff values (ECVs) for azoles used in Eastern China may offer better guidance for clinical treatments. Although ISA acts on the same target as other azoles, it may be used as an alternative therapy for cases caused by FLZ- or VRZ-resistant complex strains.
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http://dx.doi.org/10.3389/fmicb.2021.644000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969513PMC
March 2021

MicroRNA-564 inhibits the progression of non-small cell lung cancer via targeting plexin A4.

Exp Ther Med 2021 Apr 13;21(4):358. Epub 2021 Feb 13.

Department of Thoracic Surgery, Huai'an First People's Hospital, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.

Νon-small cell lung cancer (NSCLC) is the most frequently diagnosed type of cancer, and the most prevalent cause of cancer-associated mortality. The present study aimed to investigate whether microRNA (miR)-564 influences NSCLC progression by regulating NSCLC cell growth and migration, via targeting plexin A4. Therefore, the expression levels of miR-564 and plexin A4 were evaluated in NSCLC specimens or cells using reverse transcription-quantitative PCR. Furthermore, colony formation and Cell Counting Kit-8 assays were performed to determine the proliferative ability of NSCLC cells. The cell migration capacity was assessed using a Transwell assay. In addition, to examine the binding ability of miR-564 on the plexin A4 3'-untranslated region (3'UTR), a dual-luciferase reporter assay was performed. A mouse xenograft model was established to evaluate the effect of miR-564 knockdown on tumor growth , whereas the expression of plexin A4 and Ki67 in NSCLC tissues was detected using immunohistochemistry. Notably, miR-564 was downregulated in both NSCLC cell lines and tissues, while its overexpression, following transfection with miR-564 mimics, attenuated the proliferation and proliferation, migration and invasion of NSCLC cells. By contrast, silencing of miR-564 using a miR-564 inhibitor promoted NSCLC cell proliferation, migration and invasion. The luciferase assay revealed that miR-564 directly targeted the plexin A4 3'UTR in A549 and H460 cells. Additionally, the overexpression of plexin A4 rescued the effect of miR-564 on NSCLC cell proliferation, migration and invasion abilities. Further studies demonstrated that miR-564 knockdown promoted NSCLC growth, while miR-564 overexpression resulted in the opposite effect in nude mice. Overall, the results of the present study revealed that miR-564 promotes the proliferation and migration of NSCLC cells, both and , via targeting plexin A4. Therefore, miR-564 may be considered as a possible therapeutic target for NSCLC.
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http://dx.doi.org/10.3892/etm.2021.9789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903456PMC
April 2021

Quercetin induces pro-apoptotic autophagy via SIRT1/AMPK signaling pathway in human lung cancer cell lines A549 and H1299 in vitro.

Thorac Cancer 2021 Mar 11. Epub 2021 Mar 11.

Department of Respiratory and Critical Care, Tianjin Medical University General Hospital, Tianjin, China.

Background: Quercetin, a natural flavonoid compound, is a potent cancer therapeutic agent widely found in fruit and vegetables. It has been reported to induce growth inhibition and apoptosis in both A549 and H1299 human lung cancer cells. However, the effect of quercetin-induced autophagy on apoptosis and the possible autophagy mechanism in A549 and H1299 cells have not yet been critically examined.

Methods: A549 and H1299 cells were treated with different concentrations of quercetin for 24 hours. Cell growth was measured by cell counting kit-8 (CCK-8) assay, whereas apoptosis was assessed by western blotting analysis of apoptotic proteins. The levels of proteins and genes involved in autophagy were determined by western blotting and reverse transcription polymerase chain reaction (RT-PCR), respectively. Autophagosomes were also observed by transmission electron microscopy (TEM) and LC3 immunofluorescence.

Results: Quercetin inhibited cell viability and induced mitochondria-dependent apoptosis in both A549 and H1299 cells in a dose-dependent. Moreover, quercetin also promoted the expression of LC3-II and beclin 1 and suppressed the expression of p62. The mRNA levels of LC3-II, beclin 1, Atg5, Atg7, and Atg12 were upregulated by quercetin treatment. Autophagy inhibition with 3-methyladenine could effectively inhibit quercetin-induced apoptosis. In addition, quercetin dose-dependently elevated the levels of SIRT1 protein and the pAMPK-AMPK ratio. Quercetin-induced autophagy was attenuated by SIRT1 inhibitor EX527 and SirT1 knockdown by small interfering RNA (siRNA).

Conclusions: Quercetin-induced autophagy contributes to apoptosis in A549 and H1299 lung cancer cells, which involved the SIRT1/AMPK signaling pathway.
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http://dx.doi.org/10.1111/1759-7714.13925DOI Listing
March 2021

Hsa-miR-105-1 Regulates Cisplatin-Resistance in Ovarian Carcinoma Cells by Targeting ANXA9.

Anal Cell Pathol (Amst) 2021 24;2021:6662486. Epub 2021 Feb 24.

Department of Gynaecology, Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, China.

Purpose: Cisplatin is one of the most effective drugs for treating ovarian carcinoma (OC), which is among the most lethal types of carcinoma. However, the chemoresistance to cisplatin that develops over time leads to a poor clinical outcome for many OC patients. Therefore, it is necessary to clearly understand the molecular mechanisms of chemoresistance. In this study, we examined how Hsa-miR-105-1 functions in cisplatin-resistant OC cells.

Methods: The levels of Hsa-miR-105-1 expression in cisplatin-sensitive and resistant OC cell lines were detected by qRT-PCR. The target gene of Hsa-miR-105-1 was predicted by using the TargetScan and Starbase databases and verified by the double luciferase reporter gene assay. The target gene of Hsa-miR-105-1 was identified as , and expression was evaluated by qRT-PCR, western blotting, and immunofluorescence. To validate the function of Hsa-miR-105-1 in OC cells, we silenced or overexpressed Hsa-miR-105-1 in cisplatin-sensitive or resistant OC cell lines, respectively. Furthermore, the expression levels of several apoptosis-related proteins, including P53, P21, E2F1, Bcl-2, Bax, and caspase-3, were examined by western blot analysis.

Results: The levels of Hsa-miR-105-1 expression were abnormally downregulated in cisplatin-resistant OC cells, while expression was significantly upregulated in those cells. Treatment with an Hsa-miR-105-1 inhibitor promoted the expression of ANXA9 mRNA and protein, enhanced the resistance to cisplatin, and attenuated the cell apoptosis induced by cisplatin in cisplatin-sensitive OC cells. Moreover, treatment with Hsa-miR-105-1 mimics inhibited expression, which further increased the levels of P53, P21, and Bax expression and decreased the levels of E2F1 and Bcl-2 expression, finally resulting in an increased sensitivity to cisplatin in cisplatin-resistant OC cells.

Conclusion: We found that a downregulation of Hsa-miR-105-1 expression enhanced cisplatin-resistance, while an upregulation of Hsa-miR-105-1 restored the sensitivity of OC cells to cisplatin. The Hsa-miR-105-1/ axis plays an important role in the cisplatin-resistance of OC cells.
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http://dx.doi.org/10.1155/2021/6662486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929659PMC
February 2021

TGF-β-induced α-SMA expression is mediated by C/EBPβ acetylation in human alveolar epithelial cells.

Mol Med 2021 03 4;27(1):22. Epub 2021 Mar 4.

College of Bioscience & Biotechnology, Hunan Agricultural University, Changsha, 410128, Hunan, China.

Background: Although the morbidity and mortality rates associated with idiopathic pulmonary fibrosis (IPF) are high, there is still lack of powerful and precise therapeutic options for IPF.

Object: Through in vitro model, this study sought to determine whether binding of acetylated CCAAT/enhancer binding protein β (C/EBPβ) to alpha-smooth muscle actin (α-SMA) promoter could affect the activity of the latter as well as assess if it is essential for epithelial-to-mesenchymal transition (EMT) and extracellular matrix deposition in IPF.

Methods: The expression of EMT and C/EBPβ in A549 cells treated with transforming growth factor-beta (TGF-β) as pulmonary fibrotic model was detected by western blotting and qPCR. Collagen-I expression using ELISA was performed. The luciferase activity was used to examine the activity of C/EBPβ. Knockdown of C/EBPβ was performed by siRNA. We also investigated the effect of deacetylation of C/EBPβ on EMT using sirtuin 1 (SIRT1). The binding ability of C/EBPβ with α-SMA promoter was affirmed via chromatin immunoprecipitation (ChIP) and electrophoresis mobility shift assay (EMSA). The relationship between α-SMA and acetylated C/EBPβ was determined with co-immunoprecipitation (Co-IP). SiRNA-mediated knockdown of C/EBPβ in A549 cells attenuated TGF-β1-induced myofibroblast differentiation and ECM deposition. The extent of association between acetylated C/EBPβ and α-SMA promoter was dynamically monitored.

Results: It was confirmed that deacetylation of C/EBPβ in A549 cells successfully ameliorated TGF-β1-induced EMT, as shown by reduction in α-SMA expression and excessive collagen-I accumulation.

Conclusion: The EMT and fibrotic effect of TGF-β1 is dependent on acetylated C/EBPβ-mediated regulation of α-SMA gene activity. Thus, C/EBPβ acetylation may play a central role in pulmonary fibrosis.
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http://dx.doi.org/10.1186/s10020-021-00283-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934236PMC
March 2021

Curcumin induces ferroptosis in non-small-cell lung cancer via activating autophagy.

Thorac Cancer 2021 Mar 3. Epub 2021 Mar 3.

Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China.

Background: Emerging studies showed curcumin can inhibit glioblastoma and breast cancer cells via regulating ferroptosis. However, the role of ferroptosis in the inhibitory effect of curcumin on non-small-cell lung cancer (NSCLC) remains unclear.

Methods: Cell counting kit-8 (CCK-8) assay was used to measure the viability of A549 and H1299 cells under different conditions. Cell proliferation was examined by Ki67 immunofluorescence. The morphological changes of cells and tumor tissues were observed by optical microscope and hematoxylin and eosin (H&E) staining. Intracellular reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and iron contents were determined by corresponding assay kit. The related protein expression levels were detected by western blot and immunohistochemistry. Transmission electron microscope was used to observe ultrastructure changes of A549 and H1299 cells.

Results: Curcumin inhibited tumor growth and cell proliferation, but promoted cell death. Characteristic changes of ferroptosis were observed in curcumin group, including iron overload, GSH depletion and lipid peroxidation. Meanwhile, the protein level of ACSL4 was higher and the levels of SLC7A11 and GPX4 were lower in curcumin group than that in control group. Incubation of ferroptosis inhibitors ferrostatin-1 (Fer-1) or knockdown of iron-responsive element-binding protein 2 (IREB2) notably weakened curcumin-induced anti-tumor effect and ferroptosis in A549 and H1299 cells. Further investigation suggested that curcumin induced mitochondrial membrane rupture and mitochondrial cristae decrease, increased autolysosome, increased the level of Beclin1 and LC3, and decreased the level of P62. Curcumin-induced autophagy and subsequent ferroptosis were both alleviated with autophagy inhibitor chloroquine (CQ) or siBeclin1.

Conclusion: Curcumin induced ferroptosis via activating autophagy in NSCLC, which enhanced the therapeutic effect of NSCLC.
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http://dx.doi.org/10.1111/1759-7714.13904DOI Listing
March 2021

Polydopamine-Based Surface Modification of Chlorella Microspheres for Multiple Environmental Applications.

J Nanosci Nanotechnol 2021 May;21(5):3065-3071

School of Chemical Engineering & Technology, China University of Mining and Technology, Xuzhou, Jiangsu 221116, P. R. China.

Towards addressing water pollution issues, the development of multifunctional chlorella with applications ranging from sensing pollutants to heavy metal and oil removal is described. The use of chlorella cells, which are widely abundant natural structures, leads to simple and low-cost mass production of effective functional materials. Bioinspired surface modification approaches mediated by polydopamine can endow chlorella with enhanced adsorption capacity for heavy metals, as well as superhydrophobic, fluorescence and magnetic properties according to the desired application. The resulting chlorella exhibits excellent heavy metal and oil removal ability, while magnetic propulsion and guidance allow directional motion over long distances for implementation in situ removal. Moreover, it is further demonstrated that chlorella can be used as a biosensor to detect metal ions by taking advantage of the fluorescence properties of carbon dots. Such use of chlorella provides a new way for the large-scale production of functional materials to tackle water pollution.
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http://dx.doi.org/10.1166/jnn.2021.19148DOI Listing
May 2021

A sequence-based deep learning approach to predict CTCF-mediated chromatin loop.

Brief Bioinform 2021 Feb 25. Epub 2021 Feb 25.

Informational Biology at University of Electronic Science and Technology of China.

Three-dimensional (3D) architecture of the chromosomes is of crucial importance for transcription regulation and DNA replication. Various high-throughput chromosome conformation capture-based methods have revealed that CTCF-mediated chromatin loops are a major component of 3D architecture. However, CTCF-mediated chromatin loops are cell type specific, and most chromatin interaction capture techniques are time-consuming and labor-intensive, which restricts their usage on a very large number of cell types. Genomic sequence-based computational models are sophisticated enough to capture important features of chromatin architecture and help to identify chromatin loops. In this work, we develop Deep-loop, a convolutional neural network model, to integrate k-tuple nucleotide frequency component, nucleotide pair spectrum encoding, position conservation, position scoring function and natural vector features for the prediction of chromatin loops. By a series of examination based on cross-validation, Deep-loop shows excellent performance in the identification of the chromatin loops from different cell types. The source code of Deep-loop is freely available at the repository https://github.com/linDing-group/Deep-loop.
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http://dx.doi.org/10.1093/bib/bbab031DOI Listing
February 2021

Comparison of early changes in ocular surface markers and tear inflammatory mediators after femtosecond lenticule extraction and FS-LASIK.

Int J Ophthalmol 2021 18;14(2):283-291. Epub 2021 Feb 18.

Zhongshan Ophthalmic Center and State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou 510000, Guangdong Province, China.

Aim: To compare the short-term impacts of femtosecond lenticule extraction (FLEx) and femtosecond laser-assisted laser keratomileusis (FS-LASIK) on ocular surface measures and tear inflammatory mediators.

Methods: This prospective comparative nonrandomized clinical study comprised 75 eyes (75 patients). Totally 20 male and 15 female patients (age 21.62±3.25y) with 35 eyes underwent FLEx, and 26 male and 14 female patients (age 20.18±3.59y) with 40 eyes underwent FS-LASIK. Central corneal sensitivity, noninvasive tear breakup time, corneal fluorescein staining, Schirmer I test, tear meniscus height, and ocular surface disease index were evaluated in all patients. Tear concentrations of nerve growth factor (NGF), interleukin-1α (IL-1α), transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and matrix metalloproteinase-9 (MMP-9) were assessed by multiplex antibody microarray. All measurements were performed preoperatively, and 1d, 1wk, and 1mo postoperatively.

Results: Patients who underwent FLEx exhibited a more moderate reduction in central corneal sensation and less corneal fluorescein staining than those in the FS-LASIK group 1wk after the procedure (<0.01). NGF was significantly higher 1d and 1wk after surgery in the FS-LASIK group than in the FLEx group (<0.01). By contrast, compared to those in the FLEx group, higher postoperative values and slower recovery of tear TGF-β1, IL-1α, and TNF-α concentrations were observed in the FS-LASIK group (<0.01). Tear concentrations of NGF, TGF-β1, TNF-α, and IL-1α were correlated with ocular surface changes after FLEx or FS-LASIK surgery.

Conclusion: There is less early ocular surface disruption and a reduced inflammatory response after FLEx than after FS-LASIK. NGF, TGF-β1, TNF-α, and IL-1α may contribute to the process of ocular surface recovery.
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http://dx.doi.org/10.18240/ijo.2021.02.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840371PMC
February 2021

Rapid isolation of lentivirus particles from cell culture media via a hydrophobic interaction chromatography method on a polyester, capillary-channeled polymer fiber stationary phase.

Anal Bioanal Chem 2021 Feb 19. Epub 2021 Feb 19.

Department of Chemistry, Biosystems Research Complex, Clemson University, Clemson, SC, 29634, USA.

Lentiviruses are increasingly used as gene delivery vehicles for vaccines and immunotherapies. However, the purification of clinical-grade lentivirus vectors for therapeutic use is still troublesome and limits preclinical and clinical experiments. Current purification methods such as ultracentrifugation and ultrafiltration are time consuming and do not remove all of the impurities such as cellular debris, membrane fragments, and denatured proteins from the lentiviruses. The same challenges exist in terms of their analytical characterization. Presented here is the novel demonstration of the chromatographic isolation of virus particles from culture media based on the hydrophobicity characteristics of the vesicles. A method was developed to isolate lentivirus from media using a hydrophobic interaction chromatography (HIC) method performed on a polyester, capillary-channeled polymer (PET C-CP) stationary phase and a standard liquid chromatography apparatus. The method is an extension of the approach developed in this laboratory for the isolation of extracellular vesicles (EVs). Quantitative polymerase chain reaction (qPCR) was used to verify and quantify lentiviruses in elution fractions. Load and elution mobile phase compositions were optimized to affect high efficiency and throughput. The process has been visualized via scanning electron microscopy (SEM) of the fiber surfaces following media injection, the elution of proteinaceous material, and the elution of lentiviruses. This effort has yielded a rapid (<10 min), low-cost (< $15 per column, providing multiple separations), and efficient method for the isolation/purification of lentivirus particles from cell culture media at the analytical scale.
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http://dx.doi.org/10.1007/s00216-021-03232-8DOI Listing
February 2021

Estrogen promotes lncRNA H19 expression to regulate osteogenic differentiation of BMSCs and reduce osteoporosis via miR-532-3p/SIRT1 axis.

Mol Cell Endocrinol 2021 May 9;527:111171. Epub 2021 Feb 9.

Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei Province, PR China. Electronic address:

Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) plays an essential role in bone formation. Its imbalance can lead to osteoporosis. Estrogen and long noncoding RNAs (lncRNAs) have been confirmed to participate in osteogenesis. However, the underlying mechanism remains unclear. The purpose of our study was to explore the function of lncRNA H19 in estrogen-induced osteogenic differentiation of BMSCs. The present research demonstrated that the expression levels of lncRNA H19 and SIRT1 were markedly downregulated in postmenopausal osteoporosis (PMOP), while miR-532-3p expression was obviously increased. Moreover, estrogen induced the osteogenic differentiation of BMSCs by upregulating lncRNA H19. Furthermore, our integrated experiments showed that lncRNA H19 caused a decrease in the expression of miR-532-3p, which was verified to target SIRT1 directly. Additionally, estrogen alleviated osteoporosis in OVX rats through lncRNA H19-mediated miR-532-3p/SIRT1 axis. Our findings imply that lncRNA H19 mediates estrogen-regulated osteogenic differentiation in BMSCs via miR-532-3p/SIRT1 signalling and may become a novel target for alleviating PMOP.
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http://dx.doi.org/10.1016/j.mce.2021.111171DOI Listing
May 2021

Development of Novel Mitochondrial Pyruvate Carrier Inhibitors to Treat Hair Loss.

J Med Chem 2021 Feb 3;64(4):2046-2063. Epub 2021 Feb 3.

Department of Chemistry and Biochemistry, UCLA, 607 Charles E Young Dr E, Los Angeles, California 90095, United States.

Herein, we report the synthesis and evaluation of novel analogues of UK-5099 both and for the development of mitochondrial pyruvate carrier (MPC) inhibitors to treat hair loss. A comprehensive understanding of the structure-activity relationship was obtained by varying four positions of the hit compound, namely, the alkyl group on the N1 position, substituents on the indole core, various aromatic and heteroaromatic core structures, and various Michael acceptors. The major discovery was that the inhibitors with a 3,5-bis(trifluoromethyl)benzyl group at the N1 position were shown to have much better activity than (UK-5099) to increase cellular lactate production. Additionally, analogue , possessing a 7-azaindole heterocycle, was also shown to have significant MPC inhibition activity, which further increases the chemical space for drug design. Finally, more than 10 analogues were tested on shaved mice by topical treatment and promoted obvious hair growth on mice.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01570DOI Listing
February 2021

Intermittent hypoxia-induced autophagy via AMPK/mTOR signaling pathway attenuates endothelial apoptosis and dysfunction in vitro.

Sleep Breath 2021 Jan 22. Epub 2021 Jan 22.

Department of Respiratory and Critical Care, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.

Purpose: The aim of this study was to examine whether or not intermittent hypoxia (IH) upregulated autophagy and the contributions of autophagy to endothelial apoptosis and dysfunction in human umbilical vein endothelial cells (HUVECs).

Method: HUVECs were incubated under normoxia and IH conditions. After 3-, 6-, 12-, and 24-h exposure, the autophagic vacuoles and autophagosomes were observed by transmission electron microscopy and monodansylcadaverine staining. The protein levels of autophagy-related biomarkers and AMPK/mTOR pathway were measured by Western blot. The apoptosis-related proteins and the percentage of apoptotic cells were evaluated by Western blot and flow cytometry, respectively, while the levels of endothelial function biomarkers were assessed by ELISA.

Results: IH induced autophagy, as determined by the increased numbers of the autophagic vacuoles, autophagosomes, and by the elevated levels of Beclin-1 protein, the LC3II/LC3I ratio, and p62 degradation. IH-induced autophagic flux peaked at 12-h duration and weakened at 24 h. IH increased the ratio of p-AMPK/AMPK and decreased the ratio of p-mTOR/mTOR, while compound C restored the alteration. A significant decrease in the Bcl-2 level and the Bcl-2/Bax ratio and a significant increase in the protein expression levels of Bax and cleaved caspase 3 and in the percentage of apoptosis were observed under IH exposure. Moreover, the NO level was reduced, while the ET-1 and VEGF levels were raised under IH condition. These alterations were suppressed by the pretreatment of 3-methyladenine.

Conclusions: IH upregulates autophagy through AMPK/mTOR pathway in HUVECs in vitro, which might be protective against endothelial apoptosis and dysfunction caused by IH.
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http://dx.doi.org/10.1007/s11325-021-02297-0DOI Listing
January 2021

Let-7a regulates EV secretion and mitochondrial oxidative phosphorylation by targeting SNAP23 in colorectal cancer.

J Exp Clin Cancer Res 2021 Jan 14;40(1):31. Epub 2021 Jan 14.

Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.

Background: MicroRNAs (miRNAs) are abundant in tumor-derived extracellular vesicles (EVs) and the functions of extracellular miRNA to recipient cells have been extensively studied with tumorigenesis. However, the role of miRNA in EV secretion from cancer cells remains unknown.

Methods: qPCR and bioinformatics analysis were applied for determining extracellular let-7a expression from CRC patient serum and cells. Nanosight particle tracking analysis was performed for investigating the effect of let-7a on EV secretion. Luciferase reporter assays was used for identifying targeted genes synaptosome-associated protein 23 (SNAP23). In vitro and in vivo assays were used for exploring the function of let-7a/SNAP23 axis in CRC progression. Bioenergetic assays were performed for investigating the role of let-7a/SNAP23 in cellular metabolic reprogramming.

Results: let-7a miRNA was elevated in serum EVs from CRC patients and was enriched in CRC cell-derived EVs. We determined that let-7a could suppress EV secretion directly targeting SNAP23. In turn, SNAP23 promotes EV secretion of let-7a to downregulate the intracellular let-7a expression. In addition, we found a novel mechanism of let-7a/SNAP23 axis by regulating mitochondrial oxidative phosphorylation (OXPHOS) through Lin28a/SDHA signaling pathway.

Conclusions: Let-7a plays an essential role in not only inhibiting EV secretion, but also suppressing OXPHOS through SNAP23, resulting in the suppression of CRC progression, suggesting that let-7a/SNAP23 axis could provide not only effective tumor biomarkers but also novel targets for tumor therapeutic strategies.
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http://dx.doi.org/10.1186/s13046-020-01813-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807815PMC
January 2021

Overexpression of microRNA-29b inhibits epithelial-mesenchymal transition and angiogenesis of colorectal cancer through the ETV4/ERK/EGFR axis.

Cancer Cell Int 2021 Jan 6;21(1):17. Epub 2021 Jan 6.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, No. 601, Huangpu Avenue, Guangzhou, 510632, Guangdong, People's Republic of China.

Background: Recent studies have reported the involvement of microRNA-29 (miR-29) family members in human cancers through their ability to regulate cellular functions. The present study investigated biological function of miR-29b in colorectal cancer (CRC).

Methods: CRC tissues and adjacent normal tissues were collected and the expression of ETV4 and miR-29b in the tissues were identified. The relationship between ETV4 and miR-29b or ETV4 expression and the EGFR promoter was identified using dual-luciferase reporter gene and CHIP assays. The proliferation, invasion, migration, and apoptosis of CRC HCT116 cells were assayed using MTT assay, Scratch test, Transwell assay, and flow cytometry, respectively. Also, expression of epithelial-mesenchymal transition (EMT) markers, angiogenic factors, and vasculogenic mimicry formation were evaluated using RT-qPCR and Western blot.

Results: ETV4 was upregulated, while miR-29b expression was decreased in CRC tissues. ETV4 was identified as a target gene of miR-29b, which in turn inactivated the ERK signaling pathway by targeting ETV4 and inhibiting EGFR transcription. Transfection with miR-29b mimic, siRNA-ETV4, or ERK signaling pathway inhibitor U0126 increased expression of E-cadherin and TSP-1, and CRC cell apoptosis, yet reduced expression of ERK1/2, MMP-2, MMP-9, Vimentin, and VEGF, as well as inhibiting EMT, angiogenesis, and CRC cell migration and invasion. The EMT, angiogenesis and cancer progression induced by miR-29b inhibitor were reversed by siRNA-mediated ETV4 silencing.

Conclusions: miR-29b suppresses angiogenesis and EMT in CRC via the ETV4/ERK/EGFR axis.
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http://dx.doi.org/10.1186/s12935-020-01700-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789299PMC
January 2021

Analysis of Emergency Medical Rescue in the "8-12" Tianjin Port Heavy Fire Explosion Accident.

Prehosp Disaster Med 2021 Apr 5;36(2):237-242. Epub 2021 Jan 5.

Institute of Disaster Medicine, Tianjin University; Tianjin Key Laboratory for Disaster Medicine Technology, Tianjin, China.

With the progress in science and technology, hazardous chemicals are becoming more essential in chemical products, industrial and agricultural production, and daily life. Hazardous chemicals have poisoning, corrosive, explosive, and combusting natures; once on fire, they can trigger a chain of catastrophic incidences, resulting in casualties, property loss, and environmental pollution and posing hazards to life and property. Using the "8-12" explosion of the Ruihai Logistics warehouse in Tianjin Port (Binhai New District, China), the present study analyzes the characteristics of trauma of the casualties in this accident and the emergency medical rescue strategies. The goals were to improve the ability of emergency rescue in such accidents and to save people's lives and property to the maximum extent.
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http://dx.doi.org/10.1017/S1049023X20001478DOI Listing
April 2021

The importance of autophagy regulation in obstructive sleep apnea.

Sleep Breath 2021 Jan 4. Epub 2021 Jan 4.

Department of Respiratory and Critical Care, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin, 300052, China.

Purpose: Autophagy, the self-renewal process of cells, is dependent on lysosomes to degrade damaged organelles and proteins. The increased or damaged level of autophagy is proven to relate to a number of disorders, including metabolic disorders, malignant tumors, pulmonary diseases, and neurodegenerative disorders. This review aims to examine the effects of autophagy on the pathogenic mechanism of obstructive sleep apnea (OSA) in order to guide relevant disease treatment.

Methods: We conducted a search of the literature using the electronic database, focusing on articles that explored the association between OSA and autophagy.

Conclusion: OSA can induced autophagy through hypoxia, oxidative stress, endoplasmic reticulum stress, endothelial dysfunction, miRNA, etc. We propose that the mechanism of the autophagy in patients with OSA should be eclucidated in further studies.
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http://dx.doi.org/10.1007/s11325-020-02261-4DOI Listing
January 2021

The complete chloroplast genome sequence of (Hamamelidaceae).

Mitochondrial DNA B Resour 2020 Jan 20;5(1):701-702. Epub 2020 Jan 20.

Research Center for Nature Conservation and Biodiversity, State Environmental Protection Scientific Observation and Research Station for Ecology and Environment of Wuyi Mountains, State Environmental Protection Key Laboratory on Biosafety, Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment, Nanjing, China.

H.T.Chang is a critically endangered tree species endemic to southern China. In this study, we assembled and characterized the plastome of using Illumina paired-end data. The circular genome is 159,089 bp in size, consisting of two copies of inverted repeat (IR) regions of 26,235 bp, one large single-copy (LSC) region of 87,822 bp, and one small single-copy (SSC) region of 18,797 bp. It encodes a total of 114 unique genes, including 80 protein-coding genes, 30 tRNA genes, and four rRNA genes. Phylogenetic analysis based on 13 cp genome sequences indicated that was sister to the clade of and .
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http://dx.doi.org/10.1080/23802359.2019.1703606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748762PMC
January 2020

Complete mitochondrial genome and the phylogenetic position of the sp. (Crustacea, Isopod, Sphaeromatidae).

Mitochondrial DNA B Resour 2019 Nov 8;4(2):3896-3897. Epub 2019 Nov 8.

Guangxi Academy of Sciences, Guangxi Mangrove Research Center, Guangxi Key Lab of Mangrove Conservation and Utilization, Beihai, PR China.

The complete mitogenome of sp. (Crustacea, Isopod, Sphaeromatidae) was determined in this study. The total length of mitogenome was 15,839 bp, and contained 13 protein-coding genes, 21 tRNA genes, 2 rRNA genes, 1 control region, and 2 unknown fragments which longer than 200 bp. The nucleotide composition was 25.80% A, 16.56% C, 25.94% G and 31.67% T. Six initiation codons (ATA, ATC, ATG, ATT, ACG, GTG) and three termination codons (TAA, TAG, TA-) were used in the protein-coding genes. The length of tRNA genes ranged from 52 to 65 bp, and tRNA- was not identified. The phylogenetic result showed sp. was closely related to with high bootstrap value supported.
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http://dx.doi.org/10.1080/23802359.2019.1687350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707692PMC
November 2019

Laser ultrasonic imaging for defect detection on metal additive manufacturing components with rough surfaces.

Appl Opt 2020 Nov;59(33):10380-10388

Defects or discontinuities are inevitable during the melting and consolidation process of metal additive manufacturing. Online inspection of microdefects during the processing of layer-by-layer fusion is urgently needed for quality control. In this study, the laser ultrasonic C-scan imaging system is established to detect the surface defects of selective laser melting (SLM) samples that have a different surface roughness. An autosizing method based on the maximum correlation coefficient and lag time is proposed to accurately measure the defect length. The influences of the surface roughness on the laser ultrasound signal-to-noise ratio distribution and defect sizing accuracy are also studied. The results indicate that the proposed system can detect notches with a depth of 50 µm and holes with a diameter of 50 µm, comparable in size to raw powder particles. The average error for the length measurement can reach 1.5% if the notch is larger than 2 mm. Meanwhile, the sizing error of a 1 mm length notch is about 9%. In addition, there is no need to remove the rough surface of the as-built SLM samples during the detection process. Hence, we propose that the laser ultrasonic imaging system is a potential method for online inspection of metal additive manufacturing.
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http://dx.doi.org/10.1364/AO.405284DOI Listing
November 2020

Influence of coexistence of mild OSA on airway mucus hypersecretion in patients with COPD.

J Breath Res 2020 Dec 18. Epub 2020 Dec 18.

Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, CHINA.

Purpose: The coexistence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) can cause multiple system damage, and the main physiological mechanisms are continuous hypoxia and intermittent hypoxia (IH). Airway mucus hypersecretion is an important clinical feature of COPD, which can cause a progressive decline of lung function, acute COPD aggravation, and disease progression. The purpose of our study is to determine the influence of the coexistence of mild OSA on airway mucus hypersecretion.

Patients And Methods: Clinical data and airway epithelial samples were collected. The average fluorescence intensity of MUC5AC and the number of goblet cells were measured through immunofluorescence staining. MUC5AC expression was measured in human bronchial epithelial (HBE) cells exposed to normoxia, IH, particulate matter (PM), and PM+IH using real-time quantitative polymerase chain reaction and western blotting.

Results: FEV1% pred and FEV1/FVC were higher in patients with COPD-OSA overlap syndrome(OS) than in patients with COPD alone. Patients with OS had less sputum volume than patients with COPD alone.MUC5AC expression and the number of goblet cells in the airway epithelium in the COPD alone group were significantly higher than those in the OS groups. The PM+IH group had lower MUC5AC mRNA and protein expression in HBE cells than the PM group.

Conclusions: The coexistence of mild OSA may reduce goblet cell proliferation and MUC5AC expression in the airway epithelium of patients with COPD. Mild IH inhibited PM-induced up-regulation of MUC5AC expression in the mRNA and protein levels in HBE cells.
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http://dx.doi.org/10.1088/1752-7163/abd52eDOI Listing
December 2020

The Application of Machine Learning Techniques in Protein Drugs and Drug Targets Recognition (2 Version).

Authors:
Hui Ding

Curr Drug Metab 2020;21(10):778

School of Life Science and Technology, Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu, China.

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http://dx.doi.org/10.2174/138920022110201126161854DOI Listing
January 2020

Normal temperature catalytic degradation of toluene over Pt/TiO.

Environ Technol 2020 Dec 30:1-12. Epub 2020 Dec 30.

School of Environmental Science and Engineering, Tianjin University, Tianjin, People's Republic of China.

Normal temperature catalytic ozonation is an effective method for the removal of volatile organic compounds (VOCs). A series of TiO-supported noble metal catalysts were synthesized by a facile impregnation method. The as-prepared catalysts were evaluated for the catalytic oxidation of toluene. It was determined that the 1 wt%Pt/TiO exhibited outstanding performance that 65% conversion of toluene was achieved with the space velocity of 30,000 h even at room temperature (25°C). The structure-activity relationship of various catalysts was investigated via BET, XRD, SEM, TEM as well as XPS. The results indicated that the uniform dispersion of Pt nanoparticles, abundant surface adsorbed oxygen species as well as the strong interaction between Pt and TiO favoured toluene degradation at normal temperature. Based on FT-IR, a simplified reaction scheme was proposed: toluene was first oxidized to benzoate species then alcohol species, ketones, carboxyl acids, which was finally degraded into CO and HO. The low activation energy of 1 wt%Pt/TiO determined to be 47 kJ mol also benefited for toluene degradation at ambient temperature.
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http://dx.doi.org/10.1080/09593330.2020.1864482DOI Listing
December 2020

Heterojunction interface of zinc oxide and zinc sulfide promoting reactive molecules activation and carrier separation toward efficient photocatalysis.

J Colloid Interface Sci 2021 Apr 2;588:826-837. Epub 2020 Dec 2.

State Key Laboratory of Mechanical Transmissions, College of Materials Science and Engineering, Chongqing University, Chongqing 400044, China. Electronic address:

Heterojunction photocatalysts, which can alleviate the low carrier separation efficiency and insufficient light absorption capacity of a single catalyst, have received widespread attention. However, the specific interfacial structure of the heterojunction and its effect on the photocatalytic reaction is still unclear. Herein, a battery of zinc oxide/zinc sulfide (ZnO@ZnS) heterojunction microspheres with different degrees of sulfuration were successfully constructed via a facile hydrothermal method. The as-prepared photocatalysts shown decent aerobic nitric oxide (NO) oxidation performance under visible light irradiation, and the results of various characterization techniques illustrated that the superior photoactivity could be ascribed to the spatial separation of photoinduced electron-hole pairs due to the synergy of the internal electric field and the band offset. More importantly, density functional theory (DFT) calculations revealed that the heterojunction interface can significantly promote the generation of reactive oxygen species (ROS) and NO reaction intermediates and thus accelerate the photocatalytic reaction. Finally, in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) technology was used to time-dependently monitor the NO oxidation process, revealing the photocatalytic mechanism. This work investigated the role of the heterojunction interface in the gas-phase catalytic reaction, broadening the practical application of the ZnO@ZnS heterojunction.
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http://dx.doi.org/10.1016/j.jcis.2020.11.118DOI Listing
April 2021

Soil stabilization/solidification (S/S) agent---water-soluble thiourea formaldehyde (WTF) resin: Mechanism and performance with cadmium (Ⅱ).

Environ Pollut 2021 Mar 21;272:116025. Epub 2020 Nov 21.

Tianjin TEDA Greening Group Co., Ltd., China.

It is vital for the development and application of heavy metal stabilization/solidification (S/S) agents to reveal the mechanism of the reaction between water-soluble thiourea formaldehyde (WTF) resin and heavy metal and evaluate its repairing effect. Based on the density functional theory analysis of the WTF resin structure, the mechanism analysis and scanning electron microscope (SEM) showed that the three-dimensional network structure with thiocarbonyl and hydroxyl groups is very conducive to the capture of Cd. The reduction rate of Cd in soil added WTF resin could reach 70.6%-86.0%. The result of BCR's sequential extraction also proved that the 86.4%-94.1% of Cd in the soil repaired by WTF resin changed from acid-soluble state to residue state. Enzyme activity analysis and 16sRNA sequencing experiments showed that such a structure does not harm soil health. The urease and phosphatase tests showed the nitrogen and phosphorus cycle of the soil added WTF resin was repaired. Even compared with the remediation agents NaS and hydroxyapatite, WTF resin still performed better in repairing soil health. These findings provide valuable insights into the efficient causes of WTF resin and its harmless effects on soil. The results obtained provide a critical reference for the future application of practical and gentle heavy metal S/S agents.
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http://dx.doi.org/10.1016/j.envpol.2020.116025DOI Listing
March 2021

Application of antibiotics before 3 years of age increases the risk of childhood overweight and obesity.

Exp Ther Med 2021 Jan 19;21(1):56. Epub 2020 Nov 19.

Department of Pediatrics, Dongying People's Hospital, Dongying, Shandong 257000, P.R. China.

Childhood obesity and antibiotics abuse have become global health problems. It is necessary to explore the correlation between application of antibiotics for children under 3 and the risk of overweight and obesity in children. In the present study, young children aged 3 (36-38 months) were investigated using a face-to-face questionnaire survey. These children were admitted to Dongying City Children's Hospital from December 2017 to May 2019, and the effective sample size was 4,258. According to the body mass index (BMI), young children were divided into two groups, including emaciation and normal group as well as overweight and obesity group. Univariate analysis was performed to identify the possible influencing factors between the two groups using chi-square test. A difference of P<0.05 indicated statistical significance of a certain factor between the two groups, which could be adopted as an influencing factor in Logistic regression analysis. In addition, odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were employed to quantify the correlation of antibiotic application with the risk of overweight and obesity. A total of 3,322 young children (78.0%) were included in the antibiotic group while the remaining 936 (22.0%) were enrolled in the non-antibiotic group. Logistic regression analysis revealed that antibiotic application increased the risk of overweight and obesity among the 3-year-old young children (OR, 1.44; 95% CI, 1.03-2.01). In addition, application of antibiotics for five times or higher significantly increased the risk of overweight and obesity (OR, 1.73; 95% CI, 1.07-2.80), and such risks were more significant in children who were administered antibiotics for the first time within 6 months of age (OR, 1.71; 95% CI, 1.08-2.69). The application of antibiotics in infants and young children was thus revealed to increase the risk of overweight and obesity at the age of 3 in a frequency-dependent manner.
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http://dx.doi.org/10.3892/etm.2020.9488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706393PMC
January 2021

MicroRNA-219-5p participates in cyanotic congenital heart disease progression by regulating cardiomyocyte apoptosis.

Exp Ther Med 2021 Jan 11;21(1):36. Epub 2020 Nov 11.

Department of Cardiopulmonary Surgery, Huai'an First People's Hospital, Huai'an, Jiangsu 223300, P.R. China.

MicroRNAs (miRs) play important roles in the protection against and development of congenital heart disease (CHD). However, the role and potential mechanisms of miR-219-5p in cyanotic CHD remains unclear. Reverse transcription-quantitative PCR (RT-qPCR) was used to measure miR-219-5p levels in cyanotic CHD and hypoxia-induced H9C2 cells. Dual luciferase reporter gene assay was used to confirm whether liver receptor homolog-1 (LRH-1) was a direct target of miR-219-5p. miR-219-5p inhibitor and LRH-1-small interfering RNA were transfected into H9C2 cells under hypoxic conditions to investigate the role of miR-219-5p in hypoxia-induced H9C2 cells. Subsequently, cell viability was detected using an MTT assay and cell apoptosis was detected using flow cytometry. In addition, RT-qPCR and western blotting assays were performed to detect the mRNA and protein expression of LRH-1, cyclin D1 and β-catenin, respectively. The data showed that miR-219-5p expression was higher in patients with cyanotic CHD compared with patients with acyanotic CHD gradually increased in H9C2 cells with prolonged hypoxia time. Dual luciferase reporter assay results showed that LRH-1 was a direct target gene of miR-219-5p. Inhibition of miR-219-5p reversed hypoxia-induced cell viability reduction and attenuated hypoxia-induced cell apoptosis. In addition, hypoxia induction inhibited the expression of LRH-1, cyclin D1 and β-catenin, which was reversed by miR-219-5p inhibitor. However, LRH-1 downregulation reversed the miR-219-5p inhibitor enhanced cell viability, decreased cell apoptosis and increased expression of LRH-1, cyclin D1 and β-catenin in hypoxia-treated cardiomyocytes. The present results demonstrated that downregulation of miR-219-5p promoted the expression of the LRH-1/Wnt/β-catenin signaling pathway-associated components, reduced cardiomyocyte apoptosis and increased cell growth under hypoxic conditions. miR-219-5p may be a potential therapeutic target for cyanotic CHD therapy.
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http://dx.doi.org/10.3892/etm.2020.9468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690344PMC
January 2021

A novel circular RNA circ-LRIG3 facilitates the malignant progression of hepatocellular carcinoma by modulating the EZH2/STAT3 signaling.

J Exp Clin Cancer Res 2020 Nov 23;39(1):252. Epub 2020 Nov 23.

Department of GastroenterologyHenan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, 450003, Henan, China.

Background: Circular RNA (circRNA) is emerging as an important player in human diseases, especially cancer. In our previous study, we identified a series of deregulated circRNAs in hepatocellular carcinoma (HCC) by performing circRNA microarray expression profile. Here, we aimed to explore the role of circ-LRIG3 (hsa_circ_0027345) in HCC.

Methods: qRT-PCR and western blot were used to asses gene and protein expression, respectively. CCK-8, EdU and Transwell assays were used to detect cell proliferation, migration and invasion. GSEA software was applied to analyze the pathway related to circ-LRIG3. Co-IP, RIP and ChIP assays were used to identify the positive feedback axis of circ-LRIG3/EZH2/STAT3. Animal study was carried to test the role of circ-LRIG3 in vivo.

Results: Circ-LRIG3 was notably upregulated in HCC and promoted HCC cell proliferation, migration, invasion and reduced apoptosis. Circ-LRIG3 formed a ternary complex with EZH2 and STAT3, facilitating EZH2-induced STAT3 methylation and subsequent phosphorylation, resulting in the activation of STAT3 signaling. In turn, activated STAT3 could directly bind to circ-LRIG3 promoter to increase circ-LRIG3 transcription activity, thus forming a positive feedback loop. The animal models showed that exogenous expression of circ-LRIG3 enhanced tumorigenicity and metastasis in vivo, whereas these effects were blocked after treatment with C188-9, a specific STAT3 small-molecule inhibitor. Clinically, high circ-LRIG3 was closely linked with aggressive clinicopathological features and was identified as an independent risk prognostic factor of overall survival. Importantly, plasma circ-LRIG3 was found to be a highly sensitive and specific non-invasive diagnostic indicator for HCC.

Conclusions: Our study reveals the carcinogenic role of circ-LRIG3 in HCC, which may provide a new therapeutic target for HCC patients.
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http://dx.doi.org/10.1186/s13046-020-01779-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682056PMC
November 2020

Serum factor(s) from lung adenocarcinoma patients regulates the molecular clock expression.

J Cancer Res Clin Oncol 2021 Feb 21;147(2):493-498. Epub 2020 Nov 21.

Department of Neurobiology, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing, 100053, People's Republic of China.

Lung cancer is a leading cause of cancer-associated deaths worldwide. Lung cancer may lead to circadian disruption, which could contribute to the development of lung cancer. Recently, several studies using animal models indicated that tumors influence systemic circadian homeostasis in remote tissues. However, it is unclear whether carcinoma of the lungs influences remote circadian rhythm, whether this effect exists in humans, and whether signals from the tumor travel through the blood. In this study, we used a cell-based assay to determine whether serum from patients with lung adenocarcinoma could modulate the molecular clock. We found that the daily oscillation period of Bmal1 was significantly lengthened following treatment with serum from untreated lung adenocarcinoma patients. In addition, heat inactivation of this serum abolished the effect, suggesting that a heat-sensitive circulating factor(s) is present in the serum of untreated lung adenocarcinoma patients. Using real-time PCR, we also examined the mRNA abundance of Bmal1, Cry1, and Per1 in human osteosarcoma u2os cell line, HUVECs and A549 cell lines. The expression of Bmal1 was changed in A549 cells in the presence of sera from lung adenocarcinoma patients. Our study revealed a direct effect of serum from lung adenocarcinoma patients on the molecular clock.
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http://dx.doi.org/10.1007/s00432-020-03467-5DOI Listing
February 2021