Publications by authors named "Jindong Li"

85 Publications

HDAC2 enhances esophageal squamous cell carcinoma development through down-regulating microRNA-503-5p and promoting CXCL10.

Clin Epigenetics 2021 Apr 29;13(1):96. Epub 2021 Apr 29.

Department of Thoracic Surgery, The Second Hospital of Jilin University, NO. 218 Ziqiang Street, Changchun, 130041, Jilin, China.

Objective: Although esophageal squamous cell carcinoma (ESCC)-oriented mechanism has been widely explored, the integrated action of histone deacetylase 2 (HDAC2), microRNA (miR)-503-5p and C-X-C motif chemokine 10 (CXCL10) in ESCC has not been thoroughly explored. Thus, we performed the research to study the role of HDAC2/miR-503-5p/CXCL10 axis in ESCC.

Methods: ESCC tissues and mucosal tissues (5 cm from cancer tissues) were collected, in which HDAC2, miR-503-5p and CXCL10 expression levels were tested. The mechanism of HDAC2, miR-503-5p and CXCL10 was interpreted. The viability, colony formation ability, apoptosis, invasion and migration abilities of ESCC cells were tested after HDAC2, miR-503-5p or CXCL10 expression was altered. Tumorigenesis in mice was observed to further verify the in vitro effects of HDAC2 and miR-503-5p.

Results: HDAC2 and CXCL10 were up-regulated while miR-503-5p was down-regulated in ESCC. HDAC2 bound to miR-503-5p and miR-503-5p targeted CXCL10. Silencing HDAC2 or restoring miR-503-5p depressed viability, colony-forming, invasion and migration abilities and enhanced apoptosis of ESCC cells in vitro, as well as suppressed ESCC tumorigenesis in vivo. Inhibition of miR-503-5p or elevation of CXCL10 negated HDAC2 knockout-induced effects on ESCC cells.

Conclusion: This work elucidates that HDAC2 knockdown retards the process of ESCC by elevating miR-503-5p and inhibiting CXCL10 expression, which may provide a guidance for ESCC management.
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http://dx.doi.org/10.1186/s13148-021-01068-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082674PMC
April 2021

A mechanism for matrikine regulation in acute inflammatory lung injury.

JCI Insight 2021 04 8;6(7). Epub 2021 Apr 8.

Department of Medicine, Division of Pulmonology, Allergy and Critical Care Medicine, and.

Proline-glycine-proline (PGP) and its acetylated form (Ac-PGP) are neutrophil chemoattractants generated by collagen degradation, and they have been shown to play a role in chronic inflammatory disease. However, the mechanism for matrikine regulation in acute inflammation has not been well established. Here, we show that these peptides are actively transported from the lung by the oligopeptide transporter, PEPT2. Following intratracheal instillation of Ac-PGP in a mouse model, there was a rapid decline in concentration of the labeled peptide in the bronchoalveolar lavage (BAL) over time and redistribution to extrapulmonary sites. In vitro knockdown of the PEPT2 transporter in airway epithelia or use of a competitive inhibitor of PEPT2, cefadroxil, significantly reduced uptake of Ac-PGP. Animals that received intratracheal Ac-PGP plus cefadroxil had higher levels of Ac-PGP in BAL and lung tissue. Utilizing an acute LPS-induced lung injury model, we demonstrate that PEPT2 blockade enhanced pulmonary Ac-PGP levels and lung inflammation. We further validated this effect using clinical samples from patients with acute lung injury in coculture with airway epithelia. This is the first study to our knowledge to determine the in vitro and in vivo significance of active matrikine transport as a mechanism of modulating acute inflammation and to demonstrate that it may serve as a potential therapeutic target.
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http://dx.doi.org/10.1172/jci.insight.140750DOI Listing
April 2021

Microscopic structure and dynamics study of granular segregation mechanism by cyclic shear.

Sci Adv 2021 Feb 17;7(8). Epub 2021 Feb 17.

School of Physics and Astronomy, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China.

Granular mixtures with size difference can segregate upon shaking or shear. However, the quantitative study of this process remains difficult because it can be influenced by many mechanisms. Conflicting results on similar experimental systems are frequently obtained when the experimental conditions are not well controlled, which is mainly due to the fact that many mechanisms can be at work simultaneously. Moreover, it is often that macroscopic or empirical measures, which lack microscopic physical bases, are used to explain the experimental findings and therefore cannot provide an accurate and complete depiction of the overall process. Here, we carry out a detailed and systematic microscopic structure and dynamics study of a cyclically sheared granular system with rigorously controlled experimental conditions. We find that both convection and arching effect play important roles in the segregation process in our system, and we can quantitatively identify their respective contributions.
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http://dx.doi.org/10.1126/sciadv.abe8737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888927PMC
February 2021

X-Ray Tomography Investigation of Cyclically Sheared Granular Materials.

Phys Rev Lett 2021 Jan;126(4):048002

School of Physics and Astronomy, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China.

We perform combined x-ray tomography and shear force measurements on a cyclically sheared granular system with highly transient behaviors, and obtain the evolution of microscopic structures and macroscopic shear force during the shear cycle. We explain the macroscopic behaviors of the system based on microscopic processes, including particle level structural rearrangement and frictional contact variation. Specifically, we show how contact friction can induce large structural fluctuations and cause significant shear dilatancy effect for granular materials, and we also construct an empirical constitutive relationship for the macroscopic shear force.
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http://dx.doi.org/10.1103/PhysRevLett.126.048002DOI Listing
January 2021

Prolyl endopeptidase contributes to early neutrophilic inflammation in acute myocardial transplant rejection.

JCI Insight 2021 Mar 22;6(6). Epub 2021 Mar 22.

Vascular Biology and Hypertension Program.

Altered inflammation and tissue remodeling are cardinal features of cardiovascular disease and cardiac transplant rejection. Neutrophils have increasingly been understood to play a critical role in acute rejection and early allograft failure; however, discrete mechanisms that drive this damage remain poorly understood. Herein, we demonstrate that early acute cardiac rejection increases allograft prolyl endopeptidase (PE) in association with de novo production of the neutrophil proinflammatory matrikine proline-glycine-proline (PGP). In a heterotopic murine heart transplant model, PGP production and PE activity were associated with early neutrophil allograft invasion and allograft failure. Pharmacologic inhibition of PE with Z-Pro-prolinal reduced PGP, attenuated early neutrophil graft invasion, and reduced proinflammatory cytokine expression. Importantly, these changes helped preserve allograft rejection-free survival and function. Notably, within 2 independent patient cohorts, both PGP and PE activity were increased among patients with biopsy-proven rejection. The observed induction of PE and matrikine generation provide a link between neutrophilic inflammation and cardiovascular injury, represent a potential target to reduce allogenic immune responses, and uncover a mechanism of cardiovascular disease that has been previously unrecognized to our knowledge.
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http://dx.doi.org/10.1172/jci.insight.139687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026194PMC
March 2021

Hsa_circ_0000199 facilitates chemo-tolerance of triple-negative breast cancer by interfering with miR-206/613-led PI3K/Akt/mTOR signaling.

Aging (Albany NY) 2021 01 20;13(3):4522-4551. Epub 2021 Jan 20.

Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai 201100, China.

Increasing attentions have been paid to the role of circRNAs in the etiology of triple-negative breast cancer (TNBC), and we strived to figure out the association of circRNA AKT3/miRNA axis with TNBC chemo-resistance. Altogether 207 BC patients were divided into TNBC group (n=83) and non-TNBC group (n=124), and MCF-10A, MDA-MB-231, MDA-MB-468, SK-BR-3 and MCF-7 cell lines were prepared in advance. Expressions of AKT3-derived circRNAs and relevant miRNAs in the TNBC tissues and cell lines were determined by employing real-time polymerase chain reaction (PCR). It was indicated that hsa_circ_0000199 expression was higher in TNBC tissues than in non-TNBC tissues, and high hsa_circ_0000199 expression was predictive of large tumor size, advanced TNM grade, high Ki-67 level and poor 3-year survival of TNBC patients (all <0.05). Furthermore, miR-613 and miR-206 were sponged and negatively regulated by hsa_circ_0000199 (<0.001), and PI3K/Akt/mTOR signaling was depressed by si-hsa_circ_0000199 in TNBC cell lines (<0.01). Ultimately, miR-206/miR-613 inhibitor reversed impacts of si-hsa_circ_0000199 on PI3K/Akt/mTOR signaling, proliferation, migration, invasion, chemo-sensitivity and autophagy of TNBC cells (all <0.01). Conclusively, silencing of hsa_circ_0000199 enhanced TNBC chemo-sensitivity by promoting miR-206/miR-613 expression and deactivating PI3K/Akt/mTOR signaling, which was conducive to improving chemotherapeutic efficacy of TNBC patients.
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http://dx.doi.org/10.18632/aging.202415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906206PMC
January 2021

Examined lymph node count is not associated with prognosis in elderly patients with pN0 thoracic esophageal cancer.

Medicine (Baltimore) 2021 Jan;100(2):e24100

Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou.

Abstract: The purpose of this study was to determine whether the number of lymph nodes dissected predicts prognosis in surgically treated elderly patients with pN0 thoracic esophageal cancer. We searched the Surveillance, Epidemiology, and End Results database and identified the records of younger (<75 years) and older (≥75 years) patients with pN0 thoracic esophageal cancer between 1998 and 2015. The patient characteristics, tumor data, and postoperative variables were analyzed in this study. The Kaplan-Meier method and a Cox proportional hazard model were used to compare overall and cause-specific survival. Data from 1,792 esophageal cancer patients (older: n = 295; younger: n = 1497) were included. The survival analysis showed that the overall and cause-specific survival in the patients with ≥15 examined lymph nodes (eLNs) was significantly superior to that in the patients with 1 to 14 eLNs (P < .001); however, the difference disappeared in the older patients. After stratification by the tumor location, histology, pT classification, and differentiation between the younger and older cohorts to analyze the association between eLNs and survival, we found that the differences remained significant in most subgroups in the younger cohort. There were no differences in any subgroups of older patients. This study replicated the previously identified finding that long-term survival in patients with extensive lymphadenectomy was significantly superior to that in patients with less extensive lymphadenectomy. However, less extensive lymphadenectomy may be an acceptable treatment modality for elderly patients with pN0 thoracic esophageal cancer.
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http://dx.doi.org/10.1097/MD.0000000000024100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808502PMC
January 2021

Long-term outcomes of tracheal stents removal under fluoroscopy guidance: comparison of tracheal fistulas and tracheal stenosis.

BMC Pulm Med 2021 Jan 7;21(1):14. Epub 2021 Jan 7.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, No.1, East Jian She Road, Zhengzhou, 450052, China.

Background: Endoscopic removal is the most common method for removal of tracheal stents. Few studies have reported the technique of fluoroscopy-guided stent removal for tracheal fistula and tracheal stenosis. We aimed to study the safety and efficacy of fluoroscopy-guided stent removal as well as the optimal duration for stent usage.

Methods: We conducted a retrospective analysis of 152 patients who underwent fluoroscopy-guided stent removal from January 2011 to June 2017. Reasons for stent implantation were tracheal fistula in 85 patients (TF group), and tracheal stenosis in 67 patients (TS group). All patients underwent tracheal CT scans before stent removal and during follow up. The technical success rate, complications, and survival rate were compared between the two groups.

Results: The technical success rate of stent removal was 98.9 and 97.4%, respectively for the TF and TS group. Removal was routine for half of patients, and in the remainder, excessive granulation tissue was the common indications for stent removal, which was found after stenting at 142.1 ± 25.9 days in the TF group, and at 89.9 ± 15.0 day in the TS group. The total incidence of complications was 21.1 and 22.4%, respectively, for the TF and TS groups. Perioperative death occurred in one patient in the TF group, and two patients in the TS group. Recurrence of fistula or stenosis requiring re-stenting was the most comment complication in both groups. The 0.5-, 3-, 6-year survival rates were 90.3, 59.6, and 36.1% for TF group, and 80.4, 75.7, 75.7% for TS group.

Conclusions: Fluoroscopic removal of tracheal stents is safe and effective for both tracheal fistula and tracheal stenosis, with no significant difference in outcomes. Clinicians should pay attention to the risk of hemoptysis for patients with malignant tumors and a combination with endoscopic hemostasis may help improve its safety.
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http://dx.doi.org/10.1186/s12890-020-01349-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789527PMC
January 2021

Inhibited MicroRNA-301 Restrains Angiogenesis and Cell Growth in Esophageal Squamous Cell Carcinoma by Elevating PTEN.

Nanoscale Res Lett 2021 Jan 6;16(1). Epub 2021 Jan 6.

Department of Thoracic Surgery, The Second Hospital of Jilin University, No. 218 Ziqiang Street, Changchun, 130041, Jilin, China.

Objective: Esophageal squamous cell carcinoma (ESCC) is featured by early metastasis and late diagnosis. MicroRNA-301 (miR-301) is known to participate in diverse cancers. Nevertheless, effects of miR-301 on ESCC remain unexplored. Thus, we aim to explore the role of miR-301 in ESCC progression.

Methods: Expression of miR-301 and phosphatase and tensin homologue (PTEN) in ESCC tissues and cell lines was assessed. Next, the screened cells were treated with altered miR-301 or PTEN oligonucleotide and plasmid, and then, the colony formation ability, cell viability, migration, invasion, cell cycle distribution and apoptosis of ESCC cells were assessed. Moreover, tumor growth and microvessel density (MVD) were also assessed, and the targeting relationship between miR-301 and PTEN was affirmed.

Results: MiR-301 was upregulated, and PTEN was downregulated in ESCC tissues and cells. KYSE30 cells and Eca109 cells were selected for functional assays. In KYSE30 cells, inhibited miR-301 or overexpressed PTEN suppressed cell malignant behaviors, and silenced PTEN eliminated the impact of miR-301 inhibition on ESCC progression. In Eca109 cells, miR-301 overexpression or PTEN inhibition promoted cell malignant behaviors, and PTEN overexpression reversed the effects of miR-301 elevation on ESCC progression. The in vivo assay revealed that miR-301 inhibition or PTEN overexpression repressed ESCC tumor growth and MVD, and miR-301 elevation or PTEN reduction had contrary effects. Moreover, PTEN was targeted by miR-301.

Conclusion: Taken together, results in our study revealed that miR-301 affected cell growth, metastasis and angiogenesis via regulating PTEN expression in ESCC.
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http://dx.doi.org/10.1186/s11671-020-03452-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788144PMC
January 2021

Detection of Budesonide and Other Anti-Inflammatory Drugs Based on Biological Nano Sensing Technology in the Treatment of Childhood Asthma.

J Nanosci Nanotechnol 2021 Feb;21(2):1025-1031

Department of Pediatric, Hospital Affiliated 5 to Nantong University (Taizhou People's Hospital, Taizhou City, 225300, Jiangsu Province, China.

Biological nano sensing technology is a new high-tech which is a cross fusion of biology, chemistry, physics, electronics and many other fields. Biological nano sensing technology mainly uses the unique chemical properties and corresponding physical properties of biomolecules at nanometer level to detect, which greatly improves the sensitivity and flexibility of detection. The micro effect, quantum effect and corresponding macro quantum tunneling effect of nano molecules make their corresponding nano biosensors have extremely high detection performance. In this paper, the antiinflammatory drugs such as budesonide, which are used to treat children's asthma, will be measured by the biological nano sensor based on the new nano materials. The treatment of children after the inhalation of budesonide and other drugs will be measured by the biological nano sensor technology. Finally, a new research idea will be provided for the research of children's asthma pathology and related fields. In this paper, in the actual preparation of nano sensors, we mainly use functionalized carbon nanotubes to prepare sensors. The main advantage is that the price is low and easy to market and experiment promotion.
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http://dx.doi.org/10.1166/jnn.2021.18660DOI Listing
February 2021

Discovery of polypodiside as a Keap1-dependent Nrf2 activator attenuating oxidative stress and accumulation of extracellular matrix in glomerular mesangial cells under high glucose.

Bioorg Med Chem 2020 12 31;28(24):115833. Epub 2020 Oct 31.

School of Pharmacy and Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. Electronic address:

Diabetic nephropathy (DN) is a severe microvascular complication of diabetes mellitus. High glucose has resulted in oxidative stress and following renal fibrosis as the crucial nodes of this disease. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor regulating transcription of many antioxidant genes and suppressing synthesis of extracellular matrix. To discover Nrf2 activators targeting DN, we have evaluated polypodiside using cell-based assays. The results showed polypodiside inhibited the high glucose-induced self-limited proliferation of glomerular meangial cells. Activation of Nrf2 and enhanced transcription to antioxidant response elements were observed in the presence of polypodiside. Oxidative stress and accumulation of extracellular matrix induced by high glucose in glomerular meangial cells have been ameliorated by polypodiside. Further investigations revealed the effects of polypodiside on glomerular meangial cells were associated with activation of Nrf2. Co-immunoprecipitation of Nrf2 disclosed polypodiside disrupted the Kelch-like ECH-associated protein-1 (Keap1)-Nrf2 interaction. Molecular docking elucidated polypodiside could enter the Nrf2 binding cavity of Keap1 via interacting with the residues encompassing that cavity. These findings indicate polypodiside is a Keap1-dependent Nrf2 activator affording the catabatic effects against oxidative stress and accumulation of extracellular matrix in glomerular meangial cells under high glucose.
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http://dx.doi.org/10.1016/j.bmc.2020.115833DOI Listing
December 2020

Comment on "The Effect of Postoperative Complications After Minimally Invasive Esophagectomy on Long-term Survival: An International Multicenter Cohort Study".

Ann Surg 2020 Sep 28. Epub 2020 Sep 28.

Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China Department of clinical medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.

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http://dx.doi.org/10.1097/SLA.0000000000004288DOI Listing
September 2020

Wikstromol from Wikstroemia indica induces apoptosis and suppresses migration of MDA-MB-231 cells via inhibiting PI3K/Akt pathway.

J Nat Med 2021 Jan 31;75(1):178-185. Epub 2020 Aug 31.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, No. 209 Tongshan Road, Xuzhou, 221004, Jiangsu, China.

Triple negative breast cancer (TNBC) is the most severe type of breast cancer due to the lack of specific targets and rapid metastasis, which result in the poor prognosis. Recently, phosphatidylinositol 3-kinase (PI3K)/Akt pathway has emerged as a potential target for the treatment of TNBC. In our research interest to discover phytochemicals targeting TNBC, we have investigated wikstromol from Wikstroemia indica using the human TNBC MDA-MB-231 cells. The results showed wikstromol at 10 μM inhibited cell growth of MDA-MB-231 cells which was confirmed by MTT assay. Further DAPI staining has revealed wikstromol at 10 μM induced apoptosis of cancer cells, which was associated with the activation of caspase-3 following down-regulation of Bcl-2 as well as up-regulation of Bax, cleaved PARP and phosphorylated p53. Meanwhile, it was observed at 0.1 μM wikstromol suppressed the migration of the cancer cells via decreasing transcription of NF-κB and reducing activity and secretion of downstream MMP-9. In addition, p-PI3K and p-Akt were down-regulated in MDA-MB-231 cells in the presence of wikstromol at 0.1 μM, which indicated inactivation of PI3K/Akt pathway was involved in these inhibitory effects.
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http://dx.doi.org/10.1007/s11418-020-01447-0DOI Listing
January 2021

A novel chiral surfactant-type metallomicellar catalyst for asymmetric Michael addition in water.

Chem Commun (Camb) 2020 Sep 19;56(75):11118-11121. Epub 2020 Aug 19.

Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Soft Matter Chemistry & Center for Excellence in Molecular Synthesis of Chinese Academy of Sciences, Collaborative Innovation Center of Suzhou Nano Science and Technology & School of Chemistry and Materials Science in University of Science and Technology of China, Hefei, 230026, P. R. China.

A series of Schiff-based ligands consisting of both tertiary amines and lipophilic groups were designed and synthesized. Using these ligands, a new chiral surfactant-type metallomicellar catalyst was developed in water, and this was identified by SEM/TEM analyses. These metallomicelles can be empolyed in asymmetric Michael addition reactions in water, delivering the corresponding adducts with excellent yields and enantioselectivities.
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http://dx.doi.org/10.1039/d0cc04410eDOI Listing
September 2020

persists in biofilm communities in a smoke-exposed ferret model of COPD.

ERJ Open Res 2020 Jul 11;6(3). Epub 2020 Aug 11.

Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA.

Rationale: Non-typeable (NTHi) is a common inhabitant of the human nasopharynx and upper airways that can cause opportunistic infections of the airway mucosa including bronchopulmonary infections in patients with chronic obstructive pulmonary disease (COPD). It is clear that opportunistic infections contribute significantly to inflammatory exacerbations of COPD; however, there remains much to be learned regarding specific host and microbial determinants of persistence and/or clearance in this context.

Methods: In this study, we used a recently described ferret model for COPD, in which animals undergo chronic long-term exposure to cigarette smoke, to define host-pathogen interactions during COPD-related NTHi infections.

Results: NTHi bacteria colonised the lungs of smoke-exposed animals to a greater extent than controls, and elicited acute host inflammation and neutrophilic influx and activation, along with a significant increase in airway resistance and a decrease in inspiratory capacity consistent with inflammatory exacerbation; notably, these findings were not observed in air-exposed control animals. NTHi bacteria persisted within multicellular biofilm communities within the airway lumen, as evidenced by immunofluorescent detection of bacterial aggregates encased within a sialylated matrix as is typical of NTHi biofilms and differential bacterial gene expression consistent with the biofilm mode of growth.

Conclusions: Based on these results, we conclude that acute infection with NTHi initiates inflammatory exacerbation of COPD disease. The data also support the widely held hypothesis that NTHi bacteria persist within multicellular biofilm communities in the lungs of patients with COPD.
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http://dx.doi.org/10.1183/23120541.00200-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418822PMC
July 2020

Discovery of a coumarin derivative as Nrf2 activator mitigating oxidative stress and fibrosis in mesangial cells under high glucose.

Bioorg Med Chem Lett 2020 10 11;30(20):127490. Epub 2020 Aug 11.

School of Pharmacy & Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. Electronic address:

Diabetic nephropathy (DN) is a severe microvascular complication of diabetes mellitus. Oxidative stress and fibrosis largely contribute to the progression of DN. Recently, Nrf2 was found to be a potential target preventing DN. In the discovery of novel Nrf2 activators for the treatment of DN, we have evaluated coumarin derivatives from Wikstroemi indiaca. Molecular docking results have shown compound 4 could bind to Keap1 and activate Nrf2 significantly. Cell-based assays have revealed compound 4 activated Nrf2 and attenuated oxidative stress and fibrosis induced by high glucose in mesangial cells. Meanwhile, it was validated that disruption of the interaction between Keap1 and Nrf2 was involved in the activation of Nrf2 by compound 4 in mesangial cells under high glucose.
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http://dx.doi.org/10.1016/j.bmcl.2020.127490DOI Listing
October 2020

Circular RNA circDLGAP4 is involved in lung cancer development through modulating microRNA-143/CDK1 axis.

Cell Cycle 2020 08 9;19(16):2007-2017. Epub 2020 Jul 9.

Department of Thoracic Surgery, The Second Hospital of Jilin University , Changchun, Jilin, China.

To investigate the role of circular RNA DLGAP4 (circDLGAP4) in lung cancer. circDLGAP4 expression was detected in lung cancer tissues and cell lines by PCR. The correlation between circDLGAP4 and clinicopathological characteristics of lung cancer patients was investigated. Moreover, the influences of depression of circDLGAP4 on the biological processes biological processes of lung cancer cells were explored . In addition, whether circDLGAP4 regulated lung cancer cell biological processes by sponging microRNA-143 (miR-143) to regulate cyclin-dependent kinase 1 (CDK1) expression was explored and verified in another lung cell line. CircDLGAP4 expression was remarkably elevated in lung cancer tissues and was significantly corrected with TNM stage and tumor metastasis. Suppression of circDLGAP4 inhibited the biological performances of lung cancer cells. Also, there was a negative regulatory relationship between circDLGAP4 and miR-143. Inhibition of miR-143 alleviated the influences of circDLGAP4 depression on lung cancer cell biological processes. Moreover, CDK1 was discovered as a target of miR-143, and miR-143 was involved in the process of lung cancer cell biological processes through targeting CDK1. Our findings reveal that circular RNA circDLGAP4 is involved in lung cancer development through modulating microRNA-143/CDK1 axis. circDLGAP4 may serve as a potential biomarker for the diagnosis or treatment of lung cancer.
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http://dx.doi.org/10.1080/15384101.2020.1786649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469555PMC
August 2020

Hypermethylation of lncRNA MEG3 impairs chemosensitivity of breast cancer cells.

J Clin Lab Anal 2020 Sep 3;34(9):e23369. Epub 2020 Jul 3.

Department of General Surgery, Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, China.

Background: Chemoresistance posed a barrier to successful treatment of breast cancer (BC), and lncRNA MEG3 has been documented to implicate in BC development. However, whether MEG3 methylation, which led to low MEG3 expression, was relevant to BC progression and chemoresistance remained uncertain.

Methods: In the aggregate, 374 pairs of tumor tissues and adjacent normal tissues were collected from pathologically confirmed BC patients, and four BC cell lines, including MDA-MB-231, Bcap-37, MCF-7, and SK-BR-3, were purchased. Moreover, methylation-specific polymerase chain reaction (PCR) was adopted to evaluate the methylation status of BC tissues and cell lines, and chemo-tolerance of BC cell lines was assessed by performing MTT assay. Concurrently, transwell assay and scratch assay were carried out to estimate the migratory and invasive capability of BC cell lines.

Results: Methylated MEG3, lowly expressed MEG3, large tumor size (≥2 cm), advanced TNM grade and lymphatic metastasis were potentially symbolic of poor prognosis among BC patients (P < .05). Besides, MDA-MB-231 cell line exhibited the strongest resistance against paclitaxel, adriamycin, and vinorelbine (P < .05), while MCF-7 cell line seemed more sensitive against these drugs than any other BC cell line (P < .05). Furthermore, pcDNA3.1-MEG3 and 5-Aza-dC markedly sensitized MDA-MB-231 and MCF-7 cell lines against the drug treatments (P < .05). Simultaneously, proliferation and metastasis of the BC cell lines were slowed down under the force of pcDNA3.1-MEG3 and 5-Aza-dC (P < .05).

Conclusion: Preventing methylation of MEG3 might matter in lessening BC chemoresistance, owing to its hindering proliferation and metastasis of BC cells.
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http://dx.doi.org/10.1002/jcla.23369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521317PMC
September 2020

Baicalin serves a protective role in diabetic nephropathy through preventing high glucose-induced podocyte apoptosis.

Exp Ther Med 2020 Jul 29;20(1):367-374. Epub 2020 Apr 29.

Department of Pharmacy, Hospital Affiliated 5 to Nantong University, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China.

Diabetic nephropathy (DN) is one of the late complications of diabetes, which seriously affects the lives of patients. Baicalin (BA) is a flavone glycoside that has been identified to improve renal function in patients with DN. The present study aimed to investigate the roles and mechanisms of BA in DN. For that purpose, podocytes were cultured for 48 h under conditions of high glucose (HG; 30 mM D-glucose) or normal glucose (NG; 5 mM D-glucose). Then, the cells were treated with different concentrations of BA (6.25, 12.5 and 25 µM) for 24 h. Cell viability and apoptosis were determined using an MTT assay and flow cytometry, respectively. Protein and mRNA expression levels were analyzed using western blotting and reverse transcription-quantitative PCR, respectively. BA treatment was identified to promote the viability of podocytes and suppress cell apoptosis in a dose-dependent manner. Compared with the results in the NG group, HG stimulation significantly decreased the viability of podocytes and increased the apoptotic rate, whereas BA treatment following HG stimulation increased the viability of podocytes and decreased the apoptotic rate. Moreover, the effect of BA was revealed to be associated with the sirtuin 1/NF-κB signaling pathway in DN. In conclusion, the results of the present study suggested that BA treatment may significantly decrease HG-induced podocyte apoptosis, which indicated that BA might be a promising agent for DN treatment.
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http://dx.doi.org/10.3892/etm.2020.8701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296293PMC
July 2020

Lewis Acid-Catalyzed Enantioselective Friedel-Crafts Alkylation of Pyrrole in Water.

ACS Omega 2020 Jun 11;5(21):11962-11970. Epub 2020 May 11.

Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Soft Matter Chemistry and Department of Chemistry & Collaborative Innovation Center of Suzhou Nano Science and Technology, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China.

Highly enantioselective Friedel-Crafts alkylation of pyrroles with 2-enoyl-pyridine -oxides in water/chloroform (10:1) was developed under catalysis of Lewis acid. The Friedel-Crafts alkylation products can be obtained in high yields and excellent enantioselectivities. Moreover, several control experiments were carried out to study the reaction mechanism.
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http://dx.doi.org/10.1021/acsomega.9b04115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271029PMC
June 2020

Damage to red blood cells during whole blood storage.

J Trauma Acute Care Surg 2020 08;89(2):344-350

From the Department of Pathology (J.-Y.O., M.B.M., R.P.P.), Center for Free Radical Biology (J.-Y.O., R.P.P.), Program in Protease and Matrix Biology, Division of Pulmonary, Allergy and Critical Care, Department of Medicine (X.X., J.L., K.G., A.G.), Center for Injury Science, Department of Surgery (J.O.J., J.B.H.), and Department of Anesthesiology (J.-F.-P), University of Alabama at Birmingham, Birmingham, Alabama.

Background: Transfusion with stored whole blood (WB) is increasingly routine practice to resuscitate bleeding trauma patients. Storage of packed red blood cells (pRBC) results in multiple biochemical, structural, and metabolic changes, referred to as to the storage lesion that may mediate adverse effects associated with transfusion of older RBC units. These include increased hemolysis, oxidative stress, and accelerated scavenging of nitric oxide (NO). Whether similar changes occur to stored WB is unclear and are characterized in this study.

Methods: Ten WB units, in citrate-phosphate-dextrose, were purchased from the American Red Cross and changes in hemolysis (increased free hemoglobin, heme, and microparticles), oxidative stress indexed by redox cycling of peroxiredoxin-2 (Prx-2) and NO-scavenging kinetics were determined at different storage times until expiration.

Results: Microparticle number and free hemoglobin, but not heme, increased in a storage time-dependent manner. When normalized to the initial number of RBCs in stored WB units, hemolysis rates were similar to those reported for pRBCs. Prx-2 recycling kinetics were slower at expiration compared with earlier storage times. Rates of NO dioxygenation did not change with storage, but were decreased compared with freshly isolated RBCs.

Conclusion: Storage of WB results in changes associated with the pRBC storage lesion but not for all parameters tested. The relative rate of hemolysis (indexed by free hemoglobin and microparticles) and oxidative stress was similar to that of pRBCs. However, the absolute level of hemolysis products were lower due to lower hematocrit of stored WB units. The clinical significance of these findings requires further investigation.
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http://dx.doi.org/10.1097/TA.0000000000002730DOI Listing
August 2020

Predictive Value of C-reactive Protein for Complications in Esophagectomy.

Ann Thorac Surg 2020 09 1;110(3):1097-1098. Epub 2020 Apr 1.

Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, No. 1 Jian She Rd, Zhengzhou 450052, Henan Province, China.

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http://dx.doi.org/10.1016/j.athoracsur.2020.02.062DOI Listing
September 2020

LncRNA-IUR up-regulates PTEN by sponging miR-21 to regulate cancer cell proliferation and apoptosis in esophageal squamous cell carcinoma.

Esophagus 2020 07 2;17(3):298-304. Epub 2020 Mar 2.

Department of Thoracic Surgery, The Second Hospital of Jilin University, NO. 218 Ziqiang Street, Changchun City, Jilin Province, 130041, People's Republic of China.

Backgrounds: Imatinib-up-regulated lncRNA (lncRNA-IUR) is a recently identified tumor suppressor, while its role in ESCC is unknown. This study aimed to investigate the role of lncRNA-IUR in esophageal squamous cell carcinoma (ESCC).

Methods: Between April 2011 and April 2014, the Second Hospital of Jilin University admitted a total of 98 ESCC patients, from whom the present study selected 50 cases (33 males and 17 females; 43-67 years; 54.8 ± 6.0 year). ESCC cells and transient transfections, qPCR, RNA interaction analysis, western blot, CCK-8 assay, and cell apoptosis analysis were applied.

Results: We found that IUR was down-regulated in ESCC, and low levels of IUR predicted poor survival of ESCC patients. In ESCC cells, IUR expression levels were significantly and positively correlated with PTEN mRNA. Bioinformatics analysis showed that IUR may sponge miR-21, which can target PTEN. In ESCC cells, IUR over-expression led to the increased expression levels of PTEN; while miR-21 over-expression led to decreased expression levels of PTEN. IUR and miR-21 failed to affect each other. Cell proliferation and apoptosis analysis showed that IUR and PTEN over-expression inhibited cancer cell proliferation and promoted apoptosis; while miR-21 over-expression played an opposite role. In addition, miR-21 over-expression attenuated the effects of IUR over-expression on PTEN expression and cell proliferation.

Conclusion: Therefore, IUR may up-regulate PTEN by sponging miR-21 to regulate cancer cell proliferation and apoptosis in ESCC.
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http://dx.doi.org/10.1007/s10388-020-00724-xDOI Listing
July 2020

C1q/TNF-related protein-9 alleviates airway inflammation in asthma.

Int Immunopharmacol 2020 Apr 9;81:106238. Epub 2020 Feb 9.

Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun City 130041, PR China. Electronic address:

Backgrounds: Asthma is characterized as inflammatory disorder in the respiratory system with increasing tendency. Most of the asthma patients suffered from the disease since childhood. Thus, developing novel therapeutic targets of childhood asthma is necessary. Here, we conducted the present study to investigate the effects of CTRP9 (C1q tumor necrosis factor-related protein 9), a newly identified anti-inflammatory factor, on asthma.

Methods: Sixty asthmatic children (30 moderate and 30 mild) were recruited. The mRNA level of CTRP9 in peripheral blood mononuclear cells (PBMCs) and protein level of CTRP9 in serum and induced sputum (IS) samples from asthma patients and healthy controls (HCs) were measured by qPCR and ELISA, respectively. The anti-inflammatory effects of CTRP9 was determined in vitro and potential therapeutic effect on asthma was evaluated in mouse model.

Results: The mRNA and protein levels of CTRP9 was significantly down-regulated in asthmatics than HCs. Furthermore, the expression level of CTRP9 was negatively correlated with the expression of TNF-α, IL-1β, and IL-6 in PBMCs. The CTRP9 significantly suppressed the expression of pro-inflammatory factors in PBMCs and sputum cells from asthma patients in vitro. And delivering CTRP9 into mouse model of asthma showed disease alleviation.

Conclusion: Our data here indicated that CTRP9 may alleviate airway inflammation and remodeling in asthma.
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http://dx.doi.org/10.1016/j.intimp.2020.106238DOI Listing
April 2020

Down-Regulation of miR-2053 Inhibits the Development and Progression of Esophageal Carcinoma by Targeting Fyn-Related Kinase (FRK).

Dig Dis Sci 2020 10 1;65(10):2853-2862. Epub 2020 Jan 1.

Department of Thoracic Surgery, The Second Hospital of Jilin University, No. 218 Ziqiang Street, Changchun City, 130041, Jilin Province, People's Republic of China.

Background: MicroRNAs (miRNAs) play essential roles in the regulation and pathophysiology of various types of cancers including esophageal carcinoma (ESCA). Increasing numbers of miRNAs have been identified to be important regulators in the progression of ESCA by regulating gene expression. However, functional miRNAs and the underlying mechanisms involved in ESCA need sufficient elucidation.

Aims: In the present study, the function of miR-2053 was investigated in ESCA cells.

Methods: The expression of miR-2053 was detected in four different ESCA cell lines (Eca109, Ec9706, KYSE30, and TE-1 cells) and normal cell line (HEEC) by qRT-PCR. Cell proliferation, migration, and invasion abilities after knockdown of miR-2053 were assessed by CCK-8 assay, scratch assay, and transwell assay, respectively. Cell cycle of ESCA cells was detected by flow cytometric analysis. Expression of proteins in ESCA cells was detected by Western blot analysis.

Results: The results showed that the expression of miR-2053 was remarkably up-regulated in ESCA tissues and cells lines. Down-regulation of miR-2053 markedly inhibited cell proliferation, migration, and invasion and markedly induced cell cycle arrest and cell apoptosis in ESCA cell lines. Fyn-related kinase (FRK) was a target gene of miR-2053. Moreover, down-regulation of miR-2053 mediated the protein kinase B (AKT)/mammalian target of rapamycin and Wnt3a/β-catenin signaling pathway in ESCA cell lines.

Conclusions: Our results together suggest the potential of regulating miR-2053 expression against development and progression of esophageal carcinoma by targeting FRK.
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http://dx.doi.org/10.1007/s10620-019-06015-5DOI Listing
October 2020

Interventional Protocol for Treatment of Complications after Esophagojejunostomy for Esophagogastric Carcinoma.

Gastroenterol Res Pract 2019 1;2019:1465301. Epub 2019 Dec 1.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: Anastomotic stenosis and leakage are rare complications after esophagojejunostomy. The management of complications after esophagojejunostomy remains a challenge. We evaluated the outcomes and clinical effectiveness of an alternative interventional protocol.

Objectives: To determine the safety and efficacy of interventional treatment for the management of complications after esophagojejunostomy.

Methods: This study included 24 consecutive patients with complications after esophagojejunostomy treated using interventional protocol. Patients received balloon dilation or stenting for anastomotic stenosis. Patients with anastomotic leakage received three-tube placement or retrievable covered esophageal stent placement, followed by abscess drainage, nutritional support, and anti-inflammatory treatment. The three tubes and esophageal stents were removed after leakage healing and stenosis ceased.

Results: Thirteen patients received three-tube method, and 16 patients received covered stent placement. All procedures were technically successful, except for a failure of Y-type esophageal stent placement in one patient. The median retention time of stent and abscess drainage tube was 67.5 days and 87 days, respectively. No perioperative death, esophageal rupture, or massive hemorrhage was found during procedures. During follow-up, 14 patients died of cancer recurrence, and one died of severe pulmonary infection. The 1-, 3-, 5-year survival rates were 39.5%, 23.7%, and 23.7%, respectively.

Conclusion: Interventional protocol is safe, feasible, and efficacious for treatment of complications after esophagojejunostomy.
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http://dx.doi.org/10.1155/2019/1465301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913380PMC
December 2019

Self-expanding segmental radioactive metal stents for palliation of malignant esophageal strictures.

Acta Radiol 2020 Jul 19;61(7):921-926. Epub 2019 Nov 19.

Department of Interventional Radiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China.

Background: Traditional metal stents are not always suitable for patients with circuitous malignant esophageal stricture.

Purpose: We aimed to report the safety and effectiveness of stent insertion using self-expanding segmental radioactive metal stent in the palliation of malignant esophageal stricture.

Material And Methods: We conducted a retrospective analysis of 22 consecutive patients who underwent insertion of segmental radioactive metal stents from November 2016 to March 2019. Technical success, dysphagia score, and complications were analyzed. Kaplan-Meier analysis was used to analyze the survival time.

Results: The stenting procedure was successful in all 22 patients with no procedure-related deaths. Twenty-four segmental radioactive metal stents were successfully implanted. A total of 6 (27.3%) complications were found, mainly 5 (22.7%) stent migrations. The median follow-up period was 3.3 months. Stent removal was required in 4 (12.5%) patients due to complete stent migration. The mean dysphagia score decreased significantly after stent insertion (<0.0001). During follow up, 13 patients survived with no obvious clinical symptom and nine patients died. The mean survival was 9.9 months.

Conclusion: The stenting procedure using self-expanding segmental radioactive metal stents is safe and effective in dysphagia palliation of malignant esophageal stricture.
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http://dx.doi.org/10.1177/0284185119886315DOI Listing
July 2020

An Ancient CFTR Ortholog Informs Molecular Evolution in ABC Transporters.

Dev Cell 2019 11 31;51(4):421-430.e3. Epub 2019 Oct 31.

Department of Medicine, Gregory Fleming James Cystic Fibrosis Research Center, and Program in Protease and Matrix Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Birmingham Veterans Administration Medical Center, Birmingham, AL 35233, USA. Electronic address:

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel central to the development of secretory diarrhea and cystic fibrosis. The oldest CFTR ortholog identified is from dogfish shark, which retains similar structural and functional characteristics to the mammalian protein, thereby highlighting CFTR's critical role in regulating epithelial ion transport in vertebrates. However, the identification of an early CFTR ortholog with altered structure or function would provide critical insight into the evolution of epithelial anion transport. Here, we describe the earliest known CFTR, expressed in sea lamprey (Petromyzon marinus), with unique structural features, altered kinetics of activation and sensitivity to inhibition, and altered single-channel conductance compared to human CFTR. Our data provide the earliest evolutionary evidence of CFTR, offering insight regarding changes in gene and protein structure that underpin evolution from transporter to anion channel. Importantly, these data provide a unique platform to enhance our understanding of vertebrate phylogeny over a critical period of evolutionary expansion.
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http://dx.doi.org/10.1016/j.devcel.2019.09.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665244PMC
November 2019

Neutrophil-targeted, protease-activated pulmonary drug delivery blocks airway and systemic inflammation.

JCI Insight 2019 12 5;4(23). Epub 2019 Dec 5.

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.

Pulmonary drug delivery presents a unique opportunity to target lower airway inflammation, which is often characterized by the massive recruitment of neutrophils from blood. However, specific therapies are lacking modulation of airway neutrophil function, and difficult challenges must be overcome to achieve therapeutic efficacy against pulmonary inflammation, notably drug hydrophobicity, mucociliary and macrophage-dependent clearance, and high extracellular protease burden. Here, we present a multistage, aerodynamically favorable delivery platform that uses extracellular proteolysis to its advantage to deliver nanoparticle-embedded hydrophobic drugs to neutrophils within the lower airways. Our design consists of a self-regulated nanoparticle-in-microgel system, in which microgel activation is triggered by extracellular elastase (degranulated by inflammatory neutrophils), and nanoparticles are loaded with Nexinhib20, a potent neutrophil degranulation inhibitor. Successful in vivo delivery of Nexinhib20 to the airways and into neutrophils promoted resolution of the inflammatory response by dampening neutrophil recruitment and degranulation, proinflammatory cytokine production in both airway and systemic compartments, as well as the presence of neutrophil-derived pathological extracellular vesicles in the lung fluid. Our findings showcase a new platform that overcomes challenges in pulmonary drug delivery and allows customization to match the proteolytic footprint of given diseases.
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http://dx.doi.org/10.1172/jci.insight.131468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962027PMC
December 2019

A small bifurcated self-expanding metallic stent for malignant bronchial fistula or severe stenosis around the upper left carina.

Acta Radiol 2020 May 22;61(5):613-619. Epub 2019 Sep 22.

Department of Interventional Radiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China.

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http://dx.doi.org/10.1177/0284185119875631DOI Listing
May 2020