Publications by authors named "Xiaowen Zheng"

40 Publications

Sex differences in angiotensin II-induced hypertension and kidney injury: role of AT1a receptors in the proximal tubule of the kidney.

Clin Sci (Lond) 2021 Aug;135(15):1825-1843

Department of Physiology, Tulane Hypertension and Renal Center of Excellence, Tulane University School of Medicine, New Orleans, LA 70112-2699, U.S.A.

In the present study, we tested the hypothesis that there are significant sex differences in angiotensin II (Ang II)-induced hypertension and kidney injury using male and female wildtype (WT) and proximal tubule-specific AT1a receptor knockout mice (PT-Agtr1a-/-). Twelve groups (n=8-12 per group) of adult male and female WT and PT-Agtr1a-/- mice were infused with a pressor dose of Ang II via osmotic minipump for 2 weeks (1.5 mg/kg/day, i.p.) and simultaneously treated with or without losartan (20 mg/kg/day, p.o.) to determine the respective roles of AT1a receptors in the proximal tubules versus systemic tissues. Basal systolic, diastolic, and mean arterial pressure were approximately 13 ± 3 mmHg lower (P<0.01), while basal 24-h urinary Na+, K+, and Cl- excretion were significantly higher in both male and female PT-Agtr1a-/- mice than WT controls (P<0.01) without significant sex differences between different strains. Both male and female WT and PT-Agtr1a-/- mice developed hypertension (P<0.01), and the magnitudes of the pressor responses to Ang II were similar between male and female WT and PT-Agtr1a-/- mice (n.s.). Likewise, Ang II-induced hypertension was significantly attenuated in both male and female PT-Agtr1a-/- mice (P<0.01). Furthermore, losartan attenuated the hypertensive responses to Ang II to similar extents in both male and female WT and PT-Agtr1a-/- mice. Finally, Ang II-induced kidney injury was attenuated in PT-Agtr1a-/- mice (P<0.01). In conclusion, the present study demonstrates that deletion of AT1a receptors in the proximal tubules of the kidney attenuates Ang II-induced hypertension and kidney injury without revealing significant sex differences.
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http://dx.doi.org/10.1042/CS20201574DOI Listing
August 2021

Identification of an Alveolar Macrophage-Related Core Gene Set in Acute Respiratory Distress Syndrome.

J Inflamm Res 2021 1;14:2353-2361. Epub 2021 Jun 1.

Department of Emergency Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People's Republic of China.

Purpose: Acute respiratory distress syndrome (ARDS) is a rapidly progressive diffuse lung injury that is characterized by high mortality and acute onset. The pathological mechanisms of ARDS are still unclear. But alveolar macrophages have been shown to play an important role in inflammatory responses during ARDS. We aimed to find the biomarkers for ARDS for early diagnosis, to give ARDS patients timely treatment.

Methods: Gene expression profiles were downloaded from Gene Expression Omnibus (GEO) and screened for differentially expressed genes (DEGs). The common upregulated genes in all the datasets were defined as circulating ARDS alveolar macrophage-related genes (cARDSAMGs). We performed a functional enrichment analysis to explore potential biological functions of cARDSAMGs, and we built protein-protein interaction networks. Gene set variation analysis (GSVA) was used to calculate the core gene set variation analysis (CGSVA) score for individual samples. Receiver operating characteristic (ROC) curve analysis was applied on the CGSVA score to evaluate its ability for diagnosis of ARDS.

Results: A total of 60 genes were upregulated in all ARDS datasets and were therefore denominated as cARDSAMGs. The cARDSAMGs were significantly involved in multiple inflammation-, immunity- and phagocytosis-related biological processes and pathways. In the protein-protein interaction network associated with host responses to ADRS, eight genes were identified as a core gene set: PTCRA, JAG1, C1QB, ADAM17, C1QA, MMP9, VSIG4 and TNFAIP3. ROC curve analysis showed that the CGSVA score may be considered as a biomarker for ARDS: it was significantly higher in patients with ARDS than those in healthy in both alveolar lavage fluid and whole blood.

Conclusion: The ARDS alveolar macrophage-related CGSVA score may be useful as a biomarker for ARDS.
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http://dx.doi.org/10.2147/JIR.S306136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179830PMC
June 2021

Light-induced dynamic RGD pattern for sequential modulation of macrophage phenotypes.

Bioact Mater 2021 Nov 21;6(11):4065-4072. Epub 2021 Apr 21.

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.

Due to the critical roles of macrophage in immune response and tissue repair, harnessing macrophage phenotypes dynamically to match the tissue healing process on demand attracted many attentions. Although there have developed many advanced platforms with dynamic features for cell manipulation, few studies have designed a dynamic chemical pattern to sequentially polarize macrophage phenotypes and meet the immune requirements at various tissue repair stages. Here, we propose a novel strategy for spatiotemporal manipulation of macrophage phenotypes by a UV-induced dynamic Arg-Gly-Asp (RGD) pattern. By employing a photo-patterning technique and the specific interaction between cyclodextrin (CD) and azobenzene-RGD (Azo-RGD), we prepared a polyethylene glycol-dithiol/polyethylene glycol-norbornene (PEG-SH/PEG-Nor) hydrogel with dynamic RGD-patterned surface. After irradiation with 365-nm UV light, the homogeneous RGD surface was transformed to the RGD-patterned surface which induced morphological transformation of macrophages from round to elongated and subsequent phenotypic transition from pro-inflammation to anti-inflammation. The mechanism of phenotypic polarization induced by RGD pattern was proved to be related to Rho-associated protein kinase 2 (ROCK2). Sequential modulation of macrophage phenotypes by the dynamic RGD-patterned surface provides a remote and non-invasive strategy to manipulate immune reactions and achieve optimized healing outcomes.
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http://dx.doi.org/10.1016/j.bioactmat.2021.04.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089772PMC
November 2021

Myocardial protective effect of intracoronary administration of nicorandil and alprostadil via targeted perfusion microcatheter in patients undergoing elective percutaneous coronary intervention: A randomized controlled trial.

Medicine (Baltimore) 2021 Apr;100(15):e25551

Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University.

Background: The aim of the study was to evaluate the efficacy of nicorandil and alprostadil on myocardial protection in patients undergoing elective percutaneous coronary intervention (PCI).

Methods: In this prospective, single-blinded, randomized controlled study, 90 consecutive patients scheduled for elective PCI for de novo coronary lesions were assigned to the nicorandil, alprostadil, and nitroglycerin groups in a 1:1:1 ratio. Drugs were administered intracoronary via a targeted perfusion microcatheter. The primary endpoint was the thrombolysis in myocardial infarction (TIMI) myocardial perfusion frame count (TMPFC). Additionally, the corrected TIMI frame count (cTFC), TIMI myocardial perfusion grade (TMPG), and incidence of periprocedural myocardial injury (PMI) were assessed.

Results: Both nicorandil and alprostadil were significantly effective in reducing TMPFC (114.6 ± 33.7 vs 93.4 ± 30.9, P = .016; 114.3 ± 34.3 vs 94.7 ± 33.3, P = .029, respectively). Similar findings were observed in the improvement of cTFC (20.3 ± 10.5 vs 13.5 ± 5.0, P = .003; 20.2 ± 7.4 vs 15.2 ± 5.2, P = .003, respectively) and percentage of TMPG 3 (100% vs 82.8%, P = .052; 83.3% vs 96.7%, P = .196, respectively); whereas, nitroglycerin produced a limited effect on TMPFC (114.4 ± 30.9 vs 112.1 ± 31.9, P = .739), cTFC (19.4 ± 7.2 vs 19.3 ± 7.2, P = .936), and percentage of TMPG 3 (86.7% vs 86.7%, P = 1.000). No significant difference was found in the incidence of PMI (16.7% vs 16.0% vs 27.6%, P = .537), though it was comparatively lower in the nicorandil and alprostadil groups. Furthermore, the intracoronary administration of nicorandil and alprostadil had a mild effect on blood pressure and heart rate.

Conclusions: The intracoronary administration of nicorandil and alprostadil via a targeted perfusion microcatheter was more effective in improving myocardial perfusion in patients undergoing elective PCI than nitroglycerin.
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http://dx.doi.org/10.1097/MD.0000000000025551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052047PMC
April 2021

Drug-Coated Balloon Treatment for ACS Induced by Myocardial Bridging: An Intravascular Ultrasound-Guided PCI.

CJC Open 2021 Mar 3;3(3):372-375. Epub 2020 Nov 3.

Department of Cardiology, Shanghai Chest Hospital affiliated to Shanghai Jiao Tong University, Shanghai, China.

This report describes a case of a 35-year-old man who presented with acute coronary syndrome. An angiogram and intravascular ultrasound revealed atherosclerotic stenosis in the myocardial bridging segment of the mid-left anterior descending artery. The culprit lesion was treated using a drug-coated balloon, and no residual stenosis was observed, which was later confirmed by intravascular ultrasound and optical coherence tomography at a 1-year coronary angiographic follow-up. This case provides evidence that drug-coated balloon could be a potential treatment strategy for atherosclerosis located in the myocardial bridging segment and suggests advantages of the "leave nothing behind" strategy in such clinical scenarios.
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http://dx.doi.org/10.1016/j.cjco.2020.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984997PMC
March 2021

E7-Modified Substrates to Promote Adhesion and Maintain Stemness of Mesenchymal Stem Cells.

Macromol Biosci 2021 04 22;21(4):e2000384. Epub 2021 Jan 22.

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.

Mesenchymal stem cells (MSCs) have drawn great attention in clinical applications due to the self-renewal ability, multi-differentiation potential, and low immunogenicity. However, there are challenges in the ex vivo expansion of MSCs, including low efficiency, stemness loss, and safety. Therefore, it is crucial to construct a substrate that can show an alterable affinity to MSCs, and induce efficient cell expansion with minimal stemness loss. In this study, EPLQLKM (E7)-modified substrates with tunable E7 densities are fabricated on PEGylated substrates. The PEG layer with an average thickness of 1.7 nm shows good antifouling ability. E7-modified substrates have an improving effect on adhesion and spreading of the rat bone marrow-derived mesenchymal stem cells (rBMSCs), along with the increase of E7 densities. rBMSCs on E7-modified substrates maintain the stem cell phenotypes, and shows robust proliferation and multilineage differentiation, especially on the substrates with high E7 densities. In summary, this study provides a novel strategy of E7 functionalization to promote adhesion and maintain stemness of MSCs, which holds great potentials in the functionalization of microcarriers for the expansion of MSCs.
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http://dx.doi.org/10.1002/mabi.202000384DOI Listing
April 2021

Risk factors of severe cases with COVID-19: a meta-analysis.

Epidemiol Infect 2020 08 12;148:e175. Epub 2020 Aug 12.

Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning530007, People's Republic China.

Our study aimed to systematically analyse the risk factors of coronavirus disease 2019 (COVID-19) patients with severe disease. An electronic search in eight databases to identify studies describing severe or critically ill COVID-19 patients from 1 January 2020 to 3 April 2020. In the end, we meta-analysed 40 studies involving 5872 COVID-19 patients. The average age was higher in severe COVID-19 patients (weighted mean difference; WMD = 10.69, 95%CI 7.83-13.54). Patients with severe disease showed significantly lower platelet count (WMD = -18.63, 95%CI -30.86 to -6.40) and lymphocyte count (WMD = -0.35, 95%CI -0.41 to -0.30) but higher C-reactive protein (CRP; WMD = 42.7, 95%CI 31.12-54.28), lactate dehydrogenase (LDH; WMD = 137.4, 95%CI 105.5-169.3), white blood cell count(WBC), procalcitonin(PCT), D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine(Cr). Similarly, patients who died showed significantly higher WBC, D-dimer, ALT, AST and Cr but similar platelet count and LDH as patients who survived. These results indicate that older age, low platelet count, lymphopenia, elevated levels of LDH, ALT, AST, PCT, Cr and D-dimer are associated with severity of COVID-19 and thus could be used as early identification or even prediction of disease progression.
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http://dx.doi.org/10.1017/S095026882000179XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438625PMC
August 2020

Two Gene Set Variation Index as Biomarker of Bacterial and Fungal Sepsis.

Biomed Res Int 2020 3;2020:8182358. Epub 2020 Jun 3.

Department of Emergency Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, China.

Background: The incidence of sepsis has been increasing in recent years. The molecular mechanism of different pathogenic sepsis remains elusive, and biomarkers of sepsis against different pathogens are still lacking.

Methods: The microarray data of bacterial sepsis, fungal sepsis, and mock-treated samples were applied to perform differentially expressed gene (DEG) analysis to identify a bacterial sepsis-specific gene set and a fungal sepsis-specific gene set. Functional enrichment analysis was used to explore the body's response to bacterial sepsis and fungal sepsis. Gene set variation analysis (GSVA) was used to score individual samples against the two pathogen-specific gene sets, and each sample gets a GSVA index. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of sepsis. An independent data set was used to validate the bacterial sepsis-specific GSVA index.

Results: The genes differentially expressed only in bacterial sepsis and the genes differentially expressed only in fungal sepsis were significantly involved in different biological processes (BPs) and pathways. This indicated that the body's responses to fungal sepsis and bacterial sepsis are varied. Twenty-two genes were identified as bacterial sepsis-specific genes and upregulated in bacterial sepsis, and 23 genes were identified as fungal sepsis-specific genes and upregulated in fungal sepsis. ROC curve analysis showed that both of the two pathogen sepsis-specific GSVA indexes may be a reliable biomarker for corresponding pathogen-induced sepsis (AUC = 1.000), while the mRNA of CALCA (also known as PCT) have a poor diagnostic value with AUC = 0.512 in bacterial sepsis and AUC = 0.705 in fungi sepsis. In addition, the AUC of the bacterial sepsis-specific GSVA index in the independent data set was 0.762.

Conclusion: We proposed a bacterial sepsis-specific gene set and a fungal sepsis-specific gene set; the bacterial sepsis GSVA index may be a reliable biomarker for bacterial sepsis.
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http://dx.doi.org/10.1155/2020/8182358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292977PMC
March 2021

Unsaturated polyurethane films grafted with enantiomeric polylysine promotes macrophage polarization to a M2 phenotype through PI3K/Akt1/mTOR axis.

Biomaterials 2020 07 31;246:120012. Epub 2020 Mar 31.

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou, 310058, China. Electronic address:

The immune system responds immediately to tissue trauma and to biomaterial implants under the participation of M1/M2 macrophages polarization. The surface properties of biomaterials can significantly influence the tissue repair progress through modulating the macrophage functions. In this study, the surface of poly(propylene fumarate) polyurethane films (PPFU) is grafted with a same density of enantiomeric poly-l-lysine (PPFU-g-PLL) and poly-d-lysine (PPFU-g-PDL), leading to a similar level of enhanced surface wettability for the PPFU-g-PLL and PPFU-g-PDL. The polylysine-grafted PPFU can restrict the M1 polarization, whereas promote M2 polarization of macrophages in vitro, judging from the secretion of cytokines and expression of key M1 and M2 related genes. Comparatively, the PPFU-g-PDL has a stronger effect in inducing M2 polarization in vivo, resulting in a thinner fibrous capsule surrounding the implant biomaterials. The CD44 and integrins of macrophages participate in the polarization process probably by activating focal adhesion kinase (FAK) and Rho-associated protein kinase (ROCK), and downstream PI3K/Akt1/mTOR signal axis to up regulate M2 related gene expression. This study confirms for the first time that polylysine coating is an effective method to regulate the immune response of biomaterials, and the polylysine-modified thermoplastic PPFU with the advantage to promote M2 polarization may be applied widely in regenerative medicine.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120012DOI Listing
July 2020

Near-Infrared-Triggered Dynamic Surface Topography for Sequential Modulation of Macrophage Phenotypes.

ACS Appl Mater Interfaces 2019 Nov 11;11(46):43689-43697. Epub 2019 Nov 11.

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering , Zhejiang University , Hangzhou 310027 , Zhejiang , China.

Immune response is critical to tissue repair. Designing biomaterials with immunomodulatory functions has become a promising strategy to facilitate tissue repair. Considering the key roles of macrophages in tissue repair and the significance of the balance of M1 and M2, smart biomaterials, which can harness macrophage phenotypes dynamically to match the tissue healing process on demand, have attracted a lot of attention to be set apart from the traditional anti-inflammatory biomaterials. Here, we prepare a gold nanorod-contained shape memory polycaprolactone film with dynamic surface topography, which has the ability to be transformed from flat to microgrooved under near-infrared (NIR) irradiation. Based on the close relationships between the morphologies and the phenotypes of macrophages, the NIR-triggered surface transformation induces the elongation of macrophages, and consequently the upregulated expressions of arginase-1 and IL-10 in vitro, indicating the change of macrophage phenotypes. The sequential modulation of macrophage phenotypes by dynamic surface topography is further confirmed in an in vivo implantation test. The healing-matched modulation of macrophage phenotypes by dynamic surface topography without the stimuli of cytokines offers an effective and noninvasive strategy to manipulate tissue regenerative immune reactions to achieve optimized healing outcomes.
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http://dx.doi.org/10.1021/acsami.9b14808DOI Listing
November 2019

MiR-129-5p inhibits liver cancer growth by targeting calcium calmodulin-dependent protein kinase IV (CAMK4).

Cell Death Dis 2019 10 17;10(11):789. Epub 2019 Oct 17.

Department of Emergency, the Second Affiliated Hospital of Guangxi Medical University, Nanning, China.

This study was designed to investigate the mechanism by which miR-129-5p affects the biological function of liver cancer cells. The expression levels of miR-129-5p in liver cancer tissues and cells were, respectively, determined. Crystal violet staining and flow cytometry were used to detect cell proliferation and apoptosis. Wound healing assay and transwell assay were performed to test cell migration and invasion. The target gene of miR-129-5p was analyzed and verified by bioinformatics analysis and luciferase reporter assay. Tumorigenicity assays in nude mice were used to test the antitumor ability of calcium calmodulin-dependent protein kinase IV (CAMK4). miR-129-5p was found to be underexpressed in hepatocellular cancer tissues and cells and also to inhibit liver cells proliferation, migration, and invasion and promote apoptosis. CAMK4 was a direct target for miR-129-5p and was lowly expressed in liver cancer tissues and cells. CAMK4 was also found to inhibit liver cells proliferation, migration and invasion, and promote apoptosis. CAMK4 might exert an antitumor effect by inhibiting the activation of mitogen-activated protein kinase (MAPK). MiR-129-5p was a tumor suppressor with low expression in liver cancer tissues and cells. CAMK4, which is a direct target gene of miR-129-5p, could inhibit tumor by inhibiting the activation of MAPK signaling pathway.
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http://dx.doi.org/10.1038/s41419-019-1923-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797732PMC
October 2019

Global transcriptional regulation of STAT3- and MYC-mediated sepsis-induced ARDS.

Ther Adv Respir Dis 2019 Jan-Dec;13:1753466619879840

Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, No 166 Daxuedong Road, Nanning, Guangxi 530007, People's Republic China.

Background: In recent years, sepsis-induced acute respiratory distress syndrome (ARDS) has remained a major clinical challenge for patients in intensive care units. While some progress has been reported over the years, the pathogenesis of ARDS still needs to be further expounded.

Methods: In the present study, gene set enrichment analysis, differentially expressed genes analysis, short time-series expression miner, protein-protein interaction (PPI) networks, module analysis, hypergeometric test, and functional enrichment analysis were performed in whole blood gene expression profiles of sepsis and induced-sepsis ARDS to explore the molecular mechanism of sepsis-induced ARDS.

Results: Further dysregulated genes in the process evolving from healthy control through sepsis to sepsis-induced ARDS were identified and organized into 10 functional modules based on their PPI networks. These functional modules were significantly involved in cell cycle, ubiquitin mediated proteolysis, spliceosome, and other pathways. MYC, STAT3, LEF1, and BRCA1 were potential transcription factors (TFs) regulating these modules. A TF-module-pathway global regulation network was constructed. In particular, our findings suggest that MYC and STAT3 may be the key regulatory genes in the underlying dysfunction of sepsis-induced ARDS. Receiver operating characteristic curve analysis showed the core genes in the global regulation network may be biomarkers for sepsis or sepsis-induced ARDS.

Conclusions: We found that MYC and STAT3 may be the key regulatory genes in the underlying dysfunction of sepsis-induced ARDS. .
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http://dx.doi.org/10.1177/1753466619879840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769203PMC
March 2020

Optical Device Based on a Nanopillar Array by the Pattern Transfer of an Anodic Aluminum Oxide Membrane.

ACS Appl Mater Interfaces 2019 Oct 27;11(40):36817-36823. Epub 2019 Sep 27.

State Key Laboratory of Modern Optical Instrumentation, Department of Optical Engineering , Zhejiang University , Hangzhou 310027 , China.

A simple and convenient nanofabrication method is proposed to achieve nanopillar arrays by the pattern transfer of an anodic aluminum oxide membrane, profiting from the rapid and efficient preparation process and regular hexagonal lattice patterns of the anodic aluminum oxide template. The taper angle of the nanopillar is affected by the distribution of the vapor particles during the deposition process, which is highly dependent on the material and deposition power. Based on this method, a novel scheme employing aluminum nanopillar arrays is demonstrated to realize the color tuning feature by simply varying the thickness of the top dielectric layer within a large range. The nanopillar arrays are completely covered by the thick dielectric layer atop due to the great conformality of the atomic layer deposition method that is used for the dielectric deposition. In addition, the color devices present good angular insensitivity up to 45°, resulting from the excited localized surface plasmon resonance within the metallic patches. The simple fabrication method is of great advantage to produce periodic nanostructures over large areas, which are widely used in designs and verifications of optical metasurfaces for various applications, including optical communication, imaging, sensing, and so forth.
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http://dx.doi.org/10.1021/acsami.9b10338DOI Listing
October 2019

Proximal Tubule-Specific Deletion of the NHE3 (Na/H Exchanger 3) in the Kidney Attenuates Ang II (Angiotensin II)-Induced Hypertension in Mice.

Hypertension 2019 09 29;74(3):526-535. Epub 2019 Jul 29.

From the Department of Pharmacology and Toxicology (X.C.L., D.Z., X.C., X. Zheng, C.Z., J.Z., J.L.Z.), University of Mississippi Medical Center, Jackson.

The present study directly tested the hypothesis that the NHE3 (Na/H exchanger 3) in the proximal tubules of the kidney is required for the development of Ang II (angiotensin II)-induced hypertension using PT-Nhe3 (proximal tubule-specific NHE3 knockout) mice. Specifically, PT-Nhe3 mice were generated using the SGLT2-Cre/Nhe3 approach, whereas Ang II-induced hypertension was studied in 12 groups (n=5-12 per group) of adult male and female wild-type (WT) and PT-Nhe3 mice. Under basal conditions, systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure were significantly lower in male and female PT-Nhe3 than WT mice (P<0.01). A high pressor, 1.5 mg/kg per day, intraperitoneal or a slow pressor dose of Ang II, 0.5 mg/kg per day, intraperitoneal for 2 weeks significantly increased systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure in male and female WT mice (P<0.01), but the hypertensive response to Ang II was markedly attenuated in male and female PT-Nhe3 mice (P<0.01). Ang II impaired the pressure-natriuresis response in WT mice, whereas proximal tubule-specific deletion of NHE3 improved the pressure-natriuresis response in Ang II-infused PT-Nhe3 mice (P<0.01). AT receptor blocker losartan completely blocked Ang II-induced hypertension in both WT and PT-Nhe3 mice (P<0.01). However, inhibition of nitric oxide synthase with L-N-Nitroarginine methyl ester had no effect on Ang II-induced hypertension in WT or PT-Nhe3 mice (not significant). Furthermore, Ang II-induced hypertension was significantly attenuated by an orally absorbable NHE3 inhibitor AVE0657. In conclusion, NHE3 in the proximal tubules of the kidney may be a therapeutical target in hypertension induced by Ang II or with increased NHE3 expression in the proximal tubules.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685743PMC
September 2019

A collagen scaffold loaded with human umbilical cord-derived mesenchymal stem cells facilitates endometrial regeneration and restores fertility.

Acta Biomater 2019 07 7;92:160-171. Epub 2019 May 7.

Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, No. 3 Qingchun East Road, Jianggan District, Hangzhou 310016, China. Electronic address:

In women of reproductive age, severe injuries to the endometrium are often accompanied by endometrial scar formation or intrauterine adhesions (IUAs), which can result in infertility or miscarriage. Although many approaches have been used to treat severe IUAs, high recurrence rates and endometrial thinning have limited therapeutic efficiency. In this study, a collagen scaffold (CS) loaded with human umbilical cord-derived mesenchymal stem cells (UC-MSCs) was fabricated and applied for endometrial regeneration. The CS/UC-MSCs promoted human endometrial stromal cell proliferation and inhibited apoptosis in vitro through paracrine effects. In a model of endometrial damage, transplantation with the CS/UC-MSCs maintained normal luminal structure, promoted endometrial regeneration and collagen remodeling, induced intrinsic endometrial cell proliferation and epithelium recovery, and enhanced the expression of estrogen receptor α and progesterone receptor. An improved ability of the regenerated endometrium to receive embryos was confirmed. Together, our results indicate that the CS/UC-MSCs promoted endometrial structural reconstruction and functional recovery. Topical administration of the CS/UC-MSCs after trans-cervical resection of adhesions might prevent re-adhesion, promote endometrium regeneration and improve pregnancy outcomes for patients with severe IUAs. STATEMENT OF SIGNIFICANCE: Intrauterine adhesions due to severe endometrium injuries happen frequently in clinic and become one of the crucial reasons for women's infertility or miscarriage. Therefore, how to regenerate the damaged endometrium is a big challenge. In this study, a collagen scaffold (CS) loaded with human umbilical cord-derived mesenchymal stem cells (UC-MSCs) was fabricated and applied for endometrium regeneration. Herein, UC-MSCs, known for low immunogenicity and high proliferative potential, exhibit promising potential for endometrium regeneration; and collagen scaffolds provide suitable physical support. It was proved that transplantation with CS/UC-MSCs promoted endometrial regeneration and fertility restoration. It suggested that topical administration of CS/UC-MSCs in uterus could be a promising strategy for patients suffering severe intrauterine adhesion and infertility.
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http://dx.doi.org/10.1016/j.actbio.2019.05.012DOI Listing
July 2019

Millisecond Response of Shape Memory Polymer Nanocomposite Aerogel Powered by Stretchable Graphene Framework.

ACS Nano 2019 05 29;13(5):5549-5558. Epub 2019 Apr 29.

Faculty of Biology, Chemistry and Earth Sciences, Macromolecular Chemistry II and Bayreuth Center for Colloids and Interfaces , University of Bayreuth , Universitätsstraße 30 , Bayreuth 95440 , Germany.

Shape memory polymers (SMPs) change shapes as-designed through altering the chain segment movement by external stimuli, promising wide uses in actuators, sensors, drug delivery, and deployable devices. However, the recovery speed of SMPs is still far slower than the benchmark shape memory alloys (SMAs), originating from their intrinsic poor heat transport and retarded viscoelasticity of polymer chains. In this work, monolithic nanocomposite aerogels composed of bicontinuous graphene and SMP networks are designed to promote the recovery time of SMP composites to a record value of 50 ms, comparable to the SMA case. The integration of a stretchable graphene framework as a fast energy transformation grid with ultrathin polycaprolactone nanofilms (tunable at 2.5-60 nm) enables the rapid phase transition of SMPs under electrical stimulation. The graphene-SMP nanocomposite aerogels, with a density of ∼10 mg cm, exhibit a fast response (175 ± 40 mm s), large deformation (∼100%), and a wide response bandwidth (0.1-20 Hz). The ultrafast response of SMP nanocomposite aerogels confers extensive uses in sensitive fuses, micro-oscillators, artificial muscles, actuators, and soft robotics. The design of bicontinuous ultralight aerogels can be extended to fabricate multifunctional and multiresponsive hybrid materials and devices.
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http://dx.doi.org/10.1021/acsnano.9b00428DOI Listing
May 2019

Defined Substrate by Aptamer Modification with the Balanced Properties of Selective Capture and Stemness Maintenance of Mesenchymal Stem Cells.

ACS Appl Mater Interfaces 2019 Apr 15;11(16):15170-15180. Epub 2019 Apr 15.

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering , Zhejiang University , Hangzhou 310027 , China.

The recruitment of endogenous mesenchymal stem cells (MSCs), as an alluring approach for in situ tissue regeneration, always accompanies with other types of cells. Therefore, it is of enormous value to bestow a substrate with the property of selective capture to MSCs. However, it was reported that when MSCs are cultured on a substrate with excessive affinity, their stemness diminished. Therefore, constructing a substrate with the balanced ability of selective capture and stemness maintenance becomes a big challenge. In this study, an Aptamer 19S (Apt19S)-modified substrate was fabricated by grafting Apt19S on a PEGylated glass substrate. The X-ray photoelectron spectroscopy results verified that the antifouling poly(ethylene glycol) (PEG) layer was created. Tracking by ellipsometry, the thicknesses of PEG layers were proved to increase with PEG concentration. The results of the quartz crystal microbalance also validated that the Apt19S densities could be modulated by the concentrations of the Apt19S solution. The results of the cell adhesion assay indicated that the modification of Apt19S caused a significant increase in the adhesion ratio and area of rBMSCs. Selective adhesion was confirmed by coculture of rBMSCs with macrophages and NIH3T3 cells, demonstrating that a higher proportion of rBMSCs adhered to the Apt19S-modified substrate. The results of specific capture were further confirmed by a flow model to simulate the body fluid flow. The comprehensive results of reverse transcription polymerase chain reaction, immunofluorescence staining, proliferation capacity, and differentiation assay showed that the stemness of rBMSCs was maintained better on a substrate with the appropriate Apt19S density. All of these results indicated that Apt19S modification is an effective strategy to endow a substrate with the specific capture ability of MSCs, and the balance between selective capture and stemness maintenance can be achieved by the precise regulation of the aptamer density.
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http://dx.doi.org/10.1021/acsami.9b03333DOI Listing
April 2019

Genetic and genomic evidence for an important role of the Na/H exchanger 3 in blood pressure regulation and angiotensin II-induced hypertension.

Physiol Genomics 2019 04 8;51(4):97-108. Epub 2019 Mar 8.

Laboratory of Receptor and Signal Transduction, Department of Pharmacology and Toxicology; Division of Nephrology, Internal Medicine; Cardiovascular and Renal Research Center; The University of Mississippi Medical Center , Jackson, Mississippi.

The sodium (Na)/hydrogen (H) exchanger 3 (NHE3) and sodium-potassium adenosine triphosphatase (Na/K-ATPase) are two of the most important Na transporters in the proximal tubules of the kidney. On the apical membrane side, NHE3 primarily mediates the entry of Na into and the exit of H from the proximal tubules, directly and indirectly being responsible for reabsorbing ~50% of filtered Na in the proximal tubules of the kidney. On the basolateral membrane side, Na/K-ATPase serves as a powerful engine driving Na out of, while pumping K into the proximal tubules against their concentration gradients. While the roles of NHE3 and Na/K-ATPase in proximal tubular Na transport under in vitro conditions are well recognized, their respective contributions to the basal blood pressure regulation and angiotensin II (ANG II)-induced hypertension remain poorly understood. Recently, we have been fortunate to be able to use genetically modified mouse models with global, kidney- or proximal tubule-specific deletion of NHE3 to directly determine the cause and effect relationship between NHE3, basal blood pressure homeostasis, and ANG II-induced hypertension at the whole body, kidney and/or proximal tubule levels. The purpose of this article is to review the genetic and genomic evidence for an important role of NHE3 with a focus in the regulation of basal blood pressure and ANG II-induced hypertension, as we learned from studies using global, kidney- or proximal tubule-specific NHE3 knockout mice. We hypothesize that NHE3 in the proximal tubules is necessary for maintaining basal blood pressure homeostasis and the development of ANG II-induced hypertension.
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http://dx.doi.org/10.1152/physiolgenomics.00122.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485378PMC
April 2019

3--butylphthalide exerts neuroprotective effects by enhancing anti-oxidation and attenuating mitochondrial dysfunction in an in vitro model of ischemic stroke.

Drug Des Devel Ther 2018 14;12:4261-4271. Epub 2018 Dec 14.

Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, People's Republic of China,

Purpose: This study examined whether the neuroprotective drug, 3--butylphthalide (NBP), which is used to treat ischemic stroke, prevents mitochondrial dysfunction.

Materials And Methods: PC12 neuronal cells were pretreated for 24 hours with NBP (10 μmol/L), then exposed to oxygen and glucose deprivation (OGD) for 8 hours as an in vitro model of ischemic stroke. Indices of anti-oxidative response, mitochondrial function and mitochondrial dynamics were evaluated.

Results: OGD suppressed cell viability, induced apoptosis and increased caspase-3 activity. NBP significantly reversed these effects. NBP prevented oxidative damage by increasing the activity of superoxide dismutase and lowering levels of malondialdehyde (MDA) and reactive oxygen species (ROS). At the same time, it increased expression of Nrf2, HO-1 and AMPK. NBP attenuated mitochondrial dysfunction by enhancing mitochondrial membrane potential and increasing the activity of mitochondrial respiratory chain complexes I-IV and ATPase. NBP altered the balance of proteins regulating mitochondrial fusion and division.

Conclusion: NBP exerts neuroprotective actions by enhancing anti-oxidation and attenuating mitochondrial dysfunction. Our findings provide insight into how NBP may exert neuroprotective effects in ischemic stroke and raise the possibility that it may function similarly against other neurodegenerative diseases involving mitochondrial dysfunction.
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http://dx.doi.org/10.2147/DDDT.S189472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298396PMC
April 2019

Proximal Tubule-Specific Deletion of the NHE3 (Na/H Exchanger 3) Promotes the Pressure-Natriuresis Response and Lowers Blood Pressure in Mice.

Hypertension 2018 12;72(6):1328-1336

From the Division of Nephrology, Department of Pharmacology and Toxicology and Department of Medicine, University of Mississippi Medical Center, Jackson (X.C.L., X.Z., J.Z., X.C., J.L.Z.).

The present study directly tested the hypothesis that deletion of the NHE3 (Na/H exchanger 3) selectively in the proximal tubules of the kidney lowers basal blood pressure by increasing the pressure-natriuresis response in mice. Adult male and female, age-matched wild-type (WT) littermates and proximal tubule-specific NHE3 knockout mice (PT- Nhe3; n=6-16 per group) were studied for (1) basal phenotypes of electrolytes and pH, blood pressure, and kidney function; (2) the pressure-natriuresis response using the mesenteric, celiac, and abdominal arterial occlusion technique; and (3) the natriuretic responses to acute saline expansion (0.9% NaCl, 10% body weight, intraperitoneal) or 2-week of 2% NaCl diet. Under basal conditions, PT- Nhe3 mice showed significantly lower systolic, diastolic, and mean arterial blood pressure ( P<0.01) than WT mice ( P<0.01). PT- Nhe3 mice also exhibited significantly greater diuretic ( P<0.01) and natriuretic responses than WT mice ( P<0.01), without altering 24-hour fecal Na excretion, plasma pH, Na, and bicarbonate levels. In response to increased renal perfusion pressure by 30 mm Hg, the pressure-natriuresis response increased 5-fold in WT mice ( P<0.01), but it increased 8-fold in PT- Nhe3 mice ( P<0.01). In response to 10% acute saline expansion or 2-week 2% NaCl diet, more pronounced natriuretic responses were demonstrated in PT- Nhe3 than WT mice ( P<0.01). Our results support the scientific premise and physiological relevance that NHE3 in the proximal tubules plays an essential role in maintaining basal blood pressure homeostasis, and genetic deletion of NHE3 selectively in the proximal tubules of the kidney lowers blood pressure by increasing the pressure natriuretic response.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.10884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309803PMC
December 2018

Effective, angle-independent radiative cooler based on one-dimensional photonic crystal.

Opt Express 2018 Oct;26(21):27885-27893

A simple and low-cost radiative cooler based on one-dimensional photonic crystal is proposed in this work, which has an average emissivity of 96% within the atmospheric transparency window (8-13μm). The ultra-broadband emissivity property is realized by constructing the strongly overlapped optical resonances with a tandem structure composed of two lossy materials while an additional lossless material is adopted as the top layer to reduce the Fresnel reflection of the whole structure. The maximum cooling power density of the fabricated radiative cooler can reach 113.0W/m at night. When integrated with an excellent solar reflector that can reflect 97% incident solar power, it theoretically has the maximum cooling power of 83.0 W/m in the case of solar irradiance up to 1000 W/m at noon.
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http://dx.doi.org/10.1364/OE.26.027885DOI Listing
October 2018

Intratubular and intracellular renin-angiotensin system in the kidney: a unifying perspective in blood pressure control.

Clin Sci (Lond) 2018 07 9;132(13):1383-1401. Epub 2018 Jul 9.

Laboratory of Receptor and Signal Transduction, Department of Pharmacology and Toxicology, Division of Nephrology, Internal Medicine, Cardiovascular-Renal Research Center, University of Mississippi Medical Center, Jackson, MS, U.S.A.

The renin-angiotensin system (RAS) is widely recognized as one of the most important vasoactive hormonal systems in the physiological regulation of blood pressure and the development of hypertension. This recognition is derived from, and supported by, extensive molecular, cellular, genetic, and pharmacological studies on the circulating (tissue-to-tissue), paracrine (cell-to-cell), and intracrine (intracellular, mitochondrial, nuclear) RAS during last several decades. Now, it is widely accepted that circulating and local RAS may act independently or interactively, to regulate sympathetic activity, systemic and renal hemodynamics, body salt and fluid balance, and blood pressure homeostasis. However, there remains continuous debate with respect to the specific sources of intratubular and intracellular RAS in the kidney and other tissues, the relative contributions of the circulating RAS to intratubular and intracellular RAS, and the roles of intratubular compared with intracellular RAS to the normal control of blood pressure or the development of angiotensin II (ANG II)-dependent hypertension. Based on a lecture given at the recent XI International Symposium on Vasoactive Peptides held in Horizonte, Brazil, this article reviews recent studies using mouse models with global, kidney- or proximal tubule-specific overexpression (knockin) or deletion (knockout) of components of the RAS or its receptors. Although much knowledge has been gained from cell- and tissue-specific transgenic or knockout models, a unifying and integrative approach is now required to better understand how the circulating and local intratubular/intracellular RAS act independently, or with other vasoactive systems, to regulate blood pressure, cardiovascular and kidney function.
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http://dx.doi.org/10.1042/CS20180121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383523PMC
July 2018

Neuroprotective effect of formononetin against TBI in rats via suppressing inflammatory reaction in cortical neurons.

Biomed Pharmacother 2018 Oct 11;106:349-354. Epub 2018 Jul 11.

Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, China. Electronic address:

Traumatic brain injury (TBI) refers to external force-induced brain damage, characterized with necrosis and cell loss in cerebral cortex. Interestingly, a plant-extract named formononetin (FN) is found to possess promising pharmacological activities, including cellular neuroprotection. Thus, we propose that FN may exert biological protection against TBI and discuss the underlying mechanism. In the current study, a rat TBI model was established via Feeney's classical method, followed by different concentrations of FN treatment. Nissl-special and DAPI-labeled stains were utilized to assess the proliferation of cortical neurons nearing lesioned tissue. The contents of interleukin-6 (IL6), tumor necrosis factor (TNF-α), and interleukin-10 (IL10) in serum and the cortical neurons were determined by ELISA. Further, intracephalic IL10 expression levels were detected through immunoassay and RT-PCR. Interestingly, the results exhibited within the FN-treated TBI rat model indicated elevated cortical proliferation. The levels of IL10 in serum and the cortical neurons were increased following FN treatments, while TNF-α and IL6 levels in the blood were decreased. In addition, both mRNA and protein expression levels of IL10 in the FN-treated TBI rat model were up-regulated in a dose-dependent manner. Collectively, our present findings indicate that FN provides effective neuroprotection against TBI, likely by activating IL10 expression in cortical neurons nearing lesioned tissue to inhibit neuroinflammatory reaction.
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http://dx.doi.org/10.1016/j.biopha.2018.06.041DOI Listing
October 2018

Design and Applications of Cell-Selective Surfaces and Interfaces.

Biomacromolecules 2018 06 26;19(6):1746-1763. Epub 2018 Apr 26.

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering , Zhejiang University , Hangzhou 310027 , China.

Tissue regeneration involves versatile types of cells. The accumulation and disorganized behaviors of undesired cells impair the natural healing process, leading to uncontrolled immune response, restenosis, and/or fibrosis. Cell-selective surfaces and interfaces can have specific and positive effects on desired types of cells, allowing tissue regeneration with restored structures and functions. This review outlines the importance of surfaces and interfaces of biomaterials with cell-selective properties. The chemical and biological cues including peptides, antibodies, and other molecules, physical cues such as topography and elasticity, and physiological cues referring mainly to interactions between cells-cells and cell-chemokines or cytokines are effective modulators for achieving cell selectivity upon being applied into the design of biomaterials. Cell-selective biomaterials have also shown practical significance in tissue regeneration, in particular for endothelialization, nerve regeneration, capture of stem cells, and regeneration of tissues of multiple structures and functions.
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http://dx.doi.org/10.1021/acs.biomac.8b00264DOI Listing
June 2018

Implants for orthodontic anchorage: An overview.

Medicine (Baltimore) 2018 Mar;97(13):e0232

Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology Department of Epidemiology and Bio-Statistics, School of Public Health, Peking University, Beijing, China.

Implantanchorage continues to receive much attention as an important orthodontic anchorage. Since the development of orthodontic implants, the scope of applications has continued to increase. Although multiple reviews detailing implants have been published, no comprehensive evaluations have been performed. Thus, the purpose of this study was to comprehensively evaluate the effects of implants based on data published in review articles.An electronic search of the Cochrane Library, Medline, Embase, Ebsco and Sicencedirect for reviews with "orthodontic" and "systematic review or meta analysis" in the title, abstract, keywords, or full text was performed. A subsequent manual search was then performed to identify reviews concerning orthodontic implants. A manual search of the orthodontic journals American Journal of Orthodontics and Dentofacial Orthopedics (AJODO), European Journal of Orthodontics (EJO), and Angle Othodontist was also performed. Such systematic reviews that evaluated the efficacy and safety of orthodontic implants were used to indicate success rates and molar movements.A total of 23 reviews were included in the analysis. The quality of each review was assessed using a measurement tool for Assessment of Multiple Systematic Reviews (AMSTAR), and the review chosen to summarize outcomes had a quality score of >6. Most reviews were less than moderate quality. Success rates of implants ranged in a broad scope, and movement of the maxillary first molar was superior with implants compared with traditional anchorage.
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http://dx.doi.org/10.1097/MD.0000000000010232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895382PMC
March 2018

DNA methylation profile is associated with the osteogenic potential of three distinct human odontogenic stem cells.

Signal Transduct Target Ther 2018;3. Epub 2018 Jan 12.

2Central Laboratory, School of Stomatology, Peking University, Beijing, 100081 China.

Among the various sources of human autologous stem cells, stem cells isolated from dental tissues exhibit excellent properties in tissue engineering and regenerative medicine. However, the distinct potential of these odontogenic cell lines remains unclear. In this study, we analyzed DNA methylation patterns to determine whether specific differences existed among three different odontogenic cell types. Using the HumanMethylation450 Beadchip, the whole genomes of human dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), and dental follicle progenitor cells (DFPCs) were compared. Then, the osteogenic potential of these cells was evaluated both in vitro and in vivo, and the methylation levels of certain genes related to bone formation differed among the three cell lines. values less than 0.05 were considered to indicate statistical significance. The three cell types showed highly similar DNA methylation patterns, although specific differences were identified. Gene ontology analysis revealed that one of the most significantly different gene categories was related to bone formation. Thus, expression of cell surface epitopes and osteogenic-related transcription factors as well as the bone formation capacity were compared. The results showed that compared with DFPCs and DPSCs, PDLSCs had higher transcription levels of osteogenic-related factors, a higher in vitro osteogenic potential, and an increased new bone formation capacity in vivo. In conclusion, the results of this study suggested that the differential DNA methylation profiles could be related to the osteogenic potential of these human odontogenic cell populations. Additionally, the increased osteogenic potential of PDLSCs might aid researchers or clinicians in making better choices regarding tissue regeneration and clinical therapies.
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http://dx.doi.org/10.1038/s41392-017-0001-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837092PMC
February 2021

Four-miRNA signature as a prognostic tool for lung adenocarcinoma.

Onco Targets Ther 2018 21;11:29-36. Epub 2017 Dec 21.

Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China.

Purpose: The aim of this study was to generate a novel miRNA expression signature to accurately predict prognosis for patients with lung adenocarcinoma (LUAD).

Patients And Methods: Using expression profiles downloaded from The Cancer Genome Atlas database, we identified multiple miRNAs with differential expression between LUAD and paired healthy tissues. We then evaluated the prognostic values of the differentially expressed miRNAs using univariate/multivariate Cox regression analysis. This analysis was ultimately used to construct a four-miRNA signature that effectively predicted patient survival. Finally, we analyzed potential functional roles of the target genes for these four miRNAs using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses.

Results: Based on our cutoff criteria (<0.05 and |log2FC| >1.0), we identified a total of 187 differentially expressed miRNAs, including 148 that were upregulated in LUAD tissues and 39 that were downregulated. Four miRNAs (miR-148a-5p, miR-31-5p, miR-548v, and miR-550a-5p) were independently associated with survival based on Kaplan-Meier analysis. We generated a signature index based on the expression of these four miRNAs and stratified patients into low- and high-risk groups. Patients in the high-risk group had significantly shorter survival times than those in the low-risk group (=0.002). A functional enrichment analysis suggested that the target genes of these four miRNAs were involved in protein phosphorylation and the Hippo and sphingolipid signaling pathways.

Conclusion: Taken together, our results suggest that our four-miRNA signature can be used as a prognostic tool for patients with LUAD.
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http://dx.doi.org/10.2147/OTT.S155016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743192PMC
December 2017

Increased miR-155 and heme oxygenase-1 expression is involved in the protective effects of formononetin in traumatic brain injury in rats.

Am J Transl Res 2017 15;9(12):5653-5661. Epub 2017 Dec 15.

Department of Emergency, The Second Affiliated Hospital of Guangxi Medical UniversityNanning 530007, China.

Oxidative stress has been considered a major contributing factor to traumatic brain injury (TBI). Formononetin, a phytoestrogen that belongs to the flavonoid family, is extracted from plants and herbs such as the red clover. Growing evidence demonstrates that formononetin has antioxidant properties. Therefore, formononetin has potential use in treating oxidative stress injuries in TBI. In this study, the neuroprotective and antioxidant effects of formononetin against TBI, as well as the related probable mechanisms, were investigated. The TBI model was produced in male Wistar rats through Feeney's weight-drop model. At 1 day after TBI, the neurological function score and brain water content were assessed. TUNEL assay was used to determine neuronal apoptosis. The expression levels of miR-155, HO-1, and BACH1 were measured by RT-PCR and western blotting. Consequently, our findings showed that formononetin pretreatment for 5 days significantly improved the neurological scores, reduced brain edema and inhibited neuronal apoptosis in rats after TBI. MiR-155 was substantially decreased and BACH1 expression was significantly increased in the TBI model, while pretreatment with formononetin dramatically up-regulated the expression levels of miR-155 and HO-1 and down-regulated the protein expression of BACH1 in rats after TBI. In summary, formononetin has been shown to have neuroprotective effects, and the mechanisms of this effect may be associated with its inhibition of oxidative stress and activation of Nrf2-dependent antioxidant pathways in TBI.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752915PMC
December 2017

Selective capture of mesenchymal stem cells over fibroblasts and immune cells on E7-modified collagen substrates under flow circumstances.

J Mater Chem B 2018 Jan 12;6(1):165-173. Epub 2017 Dec 12.

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.

Recruitment of endogenous mesenchymal stem cells (MSCs) has become an attractive strategy for in situ tissue regeneration. However, it is of great importance to endow an implant with a specific affinity to MSCs, for many types of cells such as immune cells and fibroblasts can also be recruited. It has been demonstrated that E7 peptides have a specific affinity to MSCs, but their selectivity for MSCs when co-cultured with other cells, especially in flow conditions, has rarely been investigated. In this study, E7-modified collagen substrates were prepared using sulfosuccinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo-SMCC) as the coupling agent. The results of X-ray photoelectron spectroscopy (XPS) and quartz crystal microbalance (QCM) proved that the densities of the immobilized E7 peptides could be modulated by changing the amounts of sulfo-SMCC. The results of cell adhesion rate, adhesion area and adhesion force demonstrated that the immobilization of E7 peptides led to a significant enhancement of the adhesion of bone marrow-derived MSCs (BMSCs) compared to RAW264.7 cells and NIH3T3 cells. The selective adhesion was verified by co-culturing BMSCs with RAW264.7 cells and NIH3T3 cells, which indicated that higher proportions of BMSCs were adhered on the E7-immobilized substrates. By mimicking in vivo flow circumstances, the selective capture of BMSCs by the E7-modified substrates was revealed by a flow model. All these results suggest that E7 immobilization might be a promising strategy for an implant to achieve a better regeneration outcome by enhancing the affinity to the recruited MSCs.
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http://dx.doi.org/10.1039/c7tb02812aDOI Listing
January 2018
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