Publications by authors named "Xiaoxin Zheng"

14 Publications

  • Page 1 of 1

Sirtuin 1 alleviates neuroinflammation-induced apoptosis after traumatic brain injury.

J Cell Mol Med 2021 Apr 8. Epub 2021 Apr 8.

Department of Neurosurgery, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, China.

Sirtuin 1 (SIRT1) plays a very important role in a wide range of biological responses, such as metabolism, inflammation and cell apoptosis. Changes in the levels of SIRT1 have been detected in the brain after traumatic brain injury (TBI). Further, SIRT1 has shown a neuroprotective effect in some models of neuronal death; however, its role and working mechanisms are not well understood in the model of TBI. This study aimed to address this issue. SIRT1-specific inhibitor (sirtinol) and activator (A3) were introduced to explore the role of SIRT1 in cell apoptosis. Results of the study suggest that SIRT1 plays an important role in neuronal apoptosis after TBI by inhibiting NF-κB, IL-6 and TNF-α deacetylation and the apoptotic pathway sequentially, possibly by alleviating neuroinflammation.
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http://dx.doi.org/10.1111/jcmm.16534DOI Listing
April 2021

Key factors leading to fatal outcomes in COVID-19 patients with cardiac injury.

Sci Rep 2021 02 18;11(1):4144. Epub 2021 Feb 18.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China.

Cardiac injury among patients with COVID-19 has been reported and is associated with a high risk of mortality, but cardiac injury may not be the leading factor related to death. The factors related to poor prognosis among COVID-19 patients with myocardial injury are still unclear. This study aimed to explore the potential key factors leading to in-hospital death among COVID-19 patients with cardiac injury. This retrospective single-center study was conducted at Renmin Hospital of Wuhan University, from January 20, 2020 to April 10, 2020, in Wuhan, China. All inpatients with confirmed COVID-19 (≥ 18 years old) and cardiac injury who had died or were discharged by April 10, 2020 were included. Demographic data and clinical and laboratory findings were collected and compared between survivors and nonsurvivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with mortality in COVID-19 patients with cardiac injury. A total of 173 COVID-19 patients with cardiac injury were included in this study, 86 were discharged and 87 died in the hospital. Multivariable regression showed increased odds of in-hospital death were associated with advanced age (odds ratio 1.12, 95% CI 1.05-1.18, per year increase; p < 0.001), coagulopathy (2.54, 1.26-5.12; p = 0·009), acute respiratory distress syndrome (16.56, 6.66-41.2; p < 0.001), and elevated hypersensitive troponin I (4.54, 1.79-11.48; p = 0.001). A high risk of in-hospital death was observed among COVID-19 patients with cardiac injury in this study. The factors related to death include advanced age, coagulopathy, acute respiratory distress syndrome and elevated levels of hypersensitive troponin I.
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http://dx.doi.org/10.1038/s41598-021-82396-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892550PMC
February 2021

Anisotropic Performance of High-Quality MAPbBr Single-Crystal Wafers.

ACS Appl Mater Interfaces 2020 Nov 9;12(46):51616-51627. Epub 2020 Nov 9.

State Key Laboratory of Crystal Materials, Shandong University, Jinan, Shandong 250100, P. R. China.

It has been proved that bulk single crystals of a halide perovskite behave much better than its polycrystalline counterparts in multiple application scenarios. Thus, the growth of large-sized and high-quality single crystals is significant to guarantee their ultimate device performances. Here, based on our recently invented settled temperature and controlled antisolvent diffusion system, improvements achieved in this work include the following: (1) We modified the growth system to optimize the control over both mass and heat transport to alleviate defect formation. State-of-the-art-quality MAPbBr crystals were grown, and from the bulk crystals, differently oriented crystalline wafers were fabricated with the full width at half-maximum of X-ray rocking curves of 40-86 arcsec. (2) The optical band gaps revealed no anisotropy on differently oriented wafers, whereas the refractive index and extinction coefficient exhibited obvious anisotropy. (3) Angle-resolved polarized Raman spectra demonstrate distinct in-plane anisotropy on (100) and (110) wafers but not on the (111) wafer. The equilibrium MA orientations are deduced to adopt the <111> direction with the antiparallel MA orientation between adjacent domains. (4) Radiation detectors fabricated on differently oriented wafers proved photoresponse anisotropy to both visible and X-ray radiation, following a general order of (100) > (110) > (111). Because anisotropy is an inevitable issue for various applications employing crystalline materials, this study, based on the clarification of the debatable intrinsic dipole configuration in the pseudocubic crystal lattice, will provide quantitative information on physicochemical property anisotropy and subsequently facilitate optimization of device performance referring to crystal orientations of halide perovskite crystals.
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http://dx.doi.org/10.1021/acsami.0c14582DOI Listing
November 2020

Renal sympathetic denervation improves myocardial apoptosis in rats with isoproterenol-induced heart failure by downregulation of tumor necrosis factor-α and nuclear factor-κB.

Exp Ther Med 2017 Nov 30;14(5):4104-4110. Epub 2017 Aug 30.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.

Chronic congestive heart failure (CHF) is the end outcome of organic heart diseases and one of the major diseases harmful to human health. Renal sympathetic denervation (RSD) is the anatomical basis of transcatheter renal sympathetic nerve ablation within the renal artery. To date, the roles of norepinephrine and angiotensin II (Ang II) in myocardial apoptosis and their underlying mechanisms have not been well explored. The aim of the present study was to verify the hypothesis that RSD is likely to inhibit myocardial apoptosis by inhibiting the release of norepinephrine and Ang II. An isoproterenol-induced CHF rat model was established, and the effects of RSD on myocardial apoptosis were examined using flow cytometry and TUNEL staining. The expression of factors associated with myocardial apoptosis, including p53, tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB), caspase-2 and -3, were measured using quantitative polymerase chain reaction and western blot analysis. The results indicated that the mRNA levels of p53, TNF-α, NF-κB, caspase-2 and -3 were significantly reduced in the myocardial tissues of rats in the CHF+RSD group when compared with the levels in the CHF+sham group (P<0.01 for all). In addition, the protein levels of p53, TNF-α, NF-κB and caspases-2 and -3 were decreased by 42.6, 41.3, 46.7, 30.0 and 35.8%, respectively, in myocardial tissues of rats in the CHF+RSD group in comparison with the CHF+sham group (P<0.01 for all). Furthermore, myocardial apoptosis was improved in rats in the CHF+RSD group compared with that in the CHF+sham group (P<0.01). In conclusion, the present study provides a theoretical basis for application of RSD in the treatment of CHF.
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http://dx.doi.org/10.3892/etm.2017.5066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658694PMC
November 2017

Renal sympathetic denervation alleviates myocardial fibrosis following isoproterenol-induced heart failure.

Mol Med Rep 2017 Oct 16;16(4):5091-5098. Epub 2017 Aug 16.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.

The aim of the present study was to determine if renal sympathetic denervation (RSD) may alleviate isoproterenol-induced left ventricle remodeling, and to identify the underlying mechanism. A total of 70 rats were randomly divided into control (n=15), sham operation (n=15), heart failure (HF) with sham operation (HF + sham; n=20) and HF with treatment (HF + RSD; n=20) groups. The HF model was established by subcutaneous injection of isoproterenol; six weeks later, 1eft ventricular internal diameter at end‑systole (LVIDs), left ventricular systolic posterior wall thickness (LVPWs), 1eft ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were measured. Plasma norepinephrine (NE), angiotensin II (Ang II) and aldosterone (ALD) levels were measured by ELISA. Myocardial collagen volume fraction (CVF) was determined by Masson's staining. Reverse transcription‑quantitative polymerase chain reaction was used to determine the mRNA expression levels of ventricular transforming growth factor‑β (TGF‑β), connective tissue growth factor (CTGF) and microRNAs (miRs), including miR‑29b, miR‑30c and miR‑133a. The results demonstrated that LVIDs and LVPWs in the HF + RSD group were significantly decreased compared with the HF + sham group. By contrast, LVFS and LVEF in the HF + RSD group were significantly increased compared with the HF + sham group. RSD significantly reduced the levels of plasma NE, Ang II and ALD. CVF in the HF + RSD group was reduced by 38.1% compared with the HF + sham group. Expression levels of TGF‑β and CTGF were decreased, whereas those of miR‑29b, miR‑30c and miR‑133a were increased, in the HF + RSD group compared with the HF + sham group. These results indicated that RSD alleviates isoproterenol‑induced left ventricle remodeling potentially via downregulation of TGF‑β/CTGF and upregulation of miR‑29b, miR‑30c and miR‑133a. RSD may therefore be an effective non‑drug therapy for the treatment of heart failure.
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http://dx.doi.org/10.3892/mmr.2017.7255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647034PMC
October 2017

Renal Sympathetic Denervation in Rats Ameliorates Cardiac Dysfunction and Fibrosis Post-Myocardial Infarction Involving MicroRNAs.

Med Sci Monit 2016 Aug 4;22:2751-60. Epub 2016 Aug 4.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (mainland).

BACKGROUND The role of renal sympathetic denervation (RSD) in ameliorating post-myocardial infarction (MI) left ventricular (LV) fibrosis via microRNA-dependent regulation of connective tissue growth factor (CTGF) remains unknown. MATERIAL AND METHODS MI and RSD were induced in Sprague-Dawley rats by ligating the left coronary artery and denervating the bilateral renal nerves, respectively. Norepinephrine, renin, angiotensin II and aldosterone in plasma, collagen, microRNA21, microRNA 101a, microRNA 133a and CTGF in heart tissue, as well as cardiac function were evaluated six weeks post-MI. RESULTS In the RSD group, parameters of cardiac function were significantly improved as evidenced by increased LV ejection fraction (p<0.01), LV end-systolic diameter (p<0.01), end-diastolic diameter (p<0.05), LV systolic pressure (p<0.05), maximal rate of pressure rise and decline (dP/dtmax and dP/dtmin, p<0.05), and decreased LV end-diastolic pressure (p<0.05) when compared with MI rats. Further, reduced collagen deposition in peri-infarct myocardium was observed in RSD-treated rats along with higher microRNA101a and microRNA133a (p<0.05) and lower microRNA21 expression (p<0.01) than in MI rats. CTGF mRNA and protein levels were decreased in LV following RSD (p<0.01), accompanied by decreased expression of norepinephrine, renin, angiotensin II and aldosterone in plasma (p<0.05) compared with untreated MI rats. CONCLUSIONS The potential therapeutic effects of RSD on post-MI LV fibrosis may be partly mediated by inhibition of CTGF expression via upregulation of microRNA 101a and microRNA 133a and downregulation of microRNA21.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982530PMC
http://dx.doi.org/10.12659/msm.898105DOI Listing
August 2016

12-Month Coronary Angiography, Intravascular Ultrasound and Histology Evaluation of a Novel Fully Bioabsorbable Poly-L-Lactic Acid/Amorphous Calcium Phosphate Scaffolds in Porcine Coronary Arteries.

J Biomed Nanotechnol 2016 Apr;12(4):743-52

Our previous studies have confirmed the superior biocompatibility of the poly-L-lactic acid/amorphous calcium phosphate (PLLA/ACP) scaffolds (PowerScaffold) compared to PLLA scaffolds and their similar 6-month radial strength compared with TAXUS stents. In order to conduct further dynamic observations on the performance of the PowerScaffold after 12-month implantation compared with the TAXUS stents. Twenty PowerScaffold and 20 TAXUS were implanted in porcine coronary arteries. At 12-month follow-up, Quantitative Coronary Angiography showed that the stent reference vessel diameter (3.19 ± 0.25 mm vs. 2.75 ± 0.22 mm, p < 0.05), the mean lumen diameter (3.07 ± 0.22 mm vs. 2.70 ± 0.17 mm, p < 0.05) and the late lumen gain (0.45 ± 0.07 mm vs. 0.06 ± 0.06 mm, p < 0.01) were all significantly greater with the PowerScaffold than the TAXUS. As well, Intravascular Ultrasound showed the stent reference vessel area (7.74 ± 0.48 mm2 vs. 6.96 ± 0.51 mm2, p < 0.05), the mean stent area (7.49 ± 0.46 mm2 vs. 6.53 ± 0.47 mm2, p < 0.05) and the mean lumen area (7.22 ± 0.50 mm2 vs. 6.00 ± 0.48 mm2, p < 0.01) were all significantly greater with the PowerScaffold than the TAXUS. The luminal patency rate of the PowerScaffold significantly increased from 72.45 ± 6.84% at 1 month to 93.54 ± 8.15% at 12 months (p < 0.01) while the TAXUS stents were associated with a non-significant decreasing trend (89.44 ± 8.44% vs. 86.53 ± 8.22%). Pathology indicated the average thickness of the struts degraded by 14.25 ± 3.04 μm at 1 month, 23.39 ± 2.45 μm at 6 months and 35.54 ± 2.20 μm at 12 months. Immunohistochemical examination showed that the expression of inflammatory factors NF-κB gradually decreased from 1-month to 12-month (36.79 ± 4.78 vs. 5.79 ± 2.85, P < 0.01). As the late lumen gain of arteries implanted with the PowerScaffold increases over time with the growth of vessels, it effectively reverse the late vascular negative remodeling observed with the TAXUS stents, providing a better option for lumen restoration treatment in clinical practice.
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http://dx.doi.org/10.1166/jbn.2016.2241DOI Listing
April 2016

The Role of Weak Interactions in the Mechano-induced Single-Crystal-to-Single-Crystal Phase Transition of 8-Hydroxyquinoline-Based Co-crystals.

Chem Asian J 2016 06 11;11(11):1682-7. Epub 2016 May 11.

State Key Laboratory of Crystal Materials, Shandong University, No. 27 Shanda South Road, Jinan, 250100, P. R. China.

Mechano-induced single-crystal-to-single-crystal (SCSC) phase transitions in crystalline materials that change their properties have received more and more attention. However, there are still too few examples to study molecular-level mechanisms in the mechano-induced SCSC phase transitions, making the systematic and in-depth understanding very difficult. We report that bis-(8-hydroxyquinolinato) palladium(II)-tetracyanoquinodimethane (PdQ2 -TCNQ) and bis-(8-hydroxyquinolinato) copper(II)-tetracyanoquinodimethane (CuQ2 -TCNQ) show very different mechano-response behaviors during the SCSC phase transition. Phase transition in CuQ2 -TCNQ can be triggered by pricking on the crystal surface, while in PdQ2 -TCNQ it can only be induced by applying pressure uniformly over the whole crystal face. The crystallography data and Hirshfeld surface analysis indicate that the weak intra-layer C-H⋅⋅⋅O, C-H⋅⋅⋅N hydrogen bonds and inter-layer stacking interactions determine the feasibility of the SCSC phase transition by mechanical stimuli. Weaker intra-layer interactions and looser inter-layer stacking make the SCSC phase transition occur much more easily in the CuQ2 -TCNQ.
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http://dx.doi.org/10.1002/asia.201600425DOI Listing
June 2016

Intramyocardial delivery of VEGF165 via a novel biodegradable hydrogel induces angiogenesis and improves cardiac function after rat myocardial infarction.

Heart Vessels 2016 Jun 4;31(6):963-75. Epub 2015 Jul 4.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.

Vascular endothelial growth factor (VEGF), an independent mitogen, has been reported to induce angiogenesis and thus attenuates the damage induced by myocardial infarction (MI). VEGF165 is the most abundant and predominant isoform of VEGF. This study investigates whether this effect could be strengthened by local intramyocardial injection of VEGF165 along with a novel biodegradable Dex-PCL-HEMA/PNIPAAm hydrogel and ascertains its possible mechanism of action. Rat models of myocardial infarction were induced by coronary artery ligation. Phosphate-buffered saline (PBS group), Dex-PCL-HEMA/PNIPAAm hydrogel (Gel group), phosphate-buffered saline containing VEGF165 (VP group), and hydrogel containing VEGF165 (VPG group) were injected into a peri-infarcted area of cardiac tissue immediately after myocardial infarction, respectively. The sham group was thoracic but without myocardial infarction. The injection of VEGF165 along with a hydrogel induced angiogenesis, reduced collagen content and MI area, inhibited cell apoptosis, increased the level of VEGF165 protein and the expression of flk-1 and flt-1, and improved cardiac function compared with the injection of either alone after MI in rats. The results suggest that injection of VEGF165 along with a hydrogel acquires more cardioprotective effects than either alone in rat with MI by sustained release of VEGF165, then may enhance the feedback between VEGF and its receptors flk-1 and flt-1.
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http://dx.doi.org/10.1007/s00380-015-0710-0DOI Listing
June 2016

In Situ Microscopic Observation of the Crystallization Process of Molecular Microparticles by Fluorescence Switching.

Angew Chem Int Ed Engl 2015 Jun 14;54(27):7976-80. Epub 2015 May 14.

State Key Laboratory of Crystal Materials, Shandong University, Jinan, Shandong 250100 (P.R. China).

To clearly understand the solid-state amorphous-to-crystalline transformation is a long-standing challenge because such crystallization occuring in confined environments is difficult to observe directly. We developed an in situ and real-time imaging procedure to record the interface evolution in a solid-state crystallization of molecular amorphous particles. The method, by employing a tetra-substituted ethene with novel morphology-dependent fluorescence, which can distinguish the interfaces between the crystalline and amorphous phase by fluorescence color, is a simple and practical method to probe the inner process of a molecular microparticle. The crystallization of amorphous microparticles in different cases was clearly recorded, where the perfect microparticles and those with defects demonstrate diverse destinies. The details disclosed in this observation will deepen the understanding for a series of solid-state crystallization that we know little about before.
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http://dx.doi.org/10.1002/anie.201503052DOI Listing
June 2015

In situ imaging of on-surface, solvent-free molecular single-crystal growth.

J Am Chem Soc 2015 Apr 10;137(15):4972-5. Epub 2015 Apr 10.

†State Key Laboratory of Crystal Materials, Shandong University, Jinan, Shandong 250100, P. R. China.

The formation of crystalline materials has been studied for more than a century. Recent discoveries about the self-assembly of many inorganic materials, involving aggregation of nanoparticle (NP) precursors or pre-nucleation clusters, challenge the simple assumptions of classical crystallization theory. The situation for organic materials is even more of a terra incognita due to their high complexity. Using in situ high-temperature atomic force microscopy during the solvent-free crystallization of an organic compound [Ni(quinolone-8-thiolate)2], we observe long-range migration of NPs on a silica substrate and their incorporation into larger crystals, suggesting a non-classical pathway in the growth of the molecular crystal.
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http://dx.doi.org/10.1021/jacs.5b02637DOI Listing
April 2015

Novel biodegradable drug-eluting stent composed of poly-L-lactic acid and amorphous calcium phosphate nanoparticles demonstrates improved structural and functional performance for coronary artery disease.

J Biomed Nanotechnol 2014 Jul;10(7):1194-204

Bioabsorbable drug-eluting stents (BDES) offer multiple advantages over a permanent bare metal stent (BMS) for coronary artery disease (CAD). However, current BDES remains two major issues: inferior radial strength and biocompatibility. PowerStent Absorb BDES, fabricated by co-formulating amorphous calcium phosphate (ACP) nanoparticles with poly-L-lactic acid (PLLA/ACP, 98/2, w/w) and 2% Paclitaxel (PAX, w/w) was designed to address these issues. Two cohorts of 6 miniature pigs were each implanted with PLLA/PAX (control, 2% PAX, w/w) or PowerStent Absorb BDES. After 1 month in-vivo study, histological analyses showed significantly reduced restenosis in the PowerStent Absorb BDES cohort relative to the control cohort (44.49 +/- 410.49% vs. 64.47 +/- 16.2%, p < 0.05). Stent recoil (21.57 +/- 5.36% vs. 33.81 +/- 11.49, P < 0.05) and inflammation (3.01 +/- 0.62 vs. 4.07 +/- 0.86, P < 0.01) were also obviously decreased. From in-vitro studies, PLLA/ACP/PAX stent tube maintained significantly greater radial strength than control group during 6 months in-vitro degradation (PLLA/ACP/PAX vs. PLLA/PAX: before hydrolysis: 82.4 +/- 1.9 N vs.74.8 +/- 3.8 N; 6 weeks: 73.9 +/- 1.8 N vs. 68.0 +/- 5.3 N; 3 months: 73.5 +/- 3.4 N vs.67.2 +/- 3.8 N; 6 months: 56.3 +/- 8.1 N vs. 57.5 +/- 4.9 N). Moreover, ACP facilitated the hydrolytic degradation of PLLA compared with control one (62.6% vs. 49.8%), meanwhile, it also increased the crystallinity of PLLA (58.4% vs. 50.7%) at 6 months. From SEM observations, ACP created nanometer pores that enlarge gradually to a micrometer scale as degradation proceeds. The changes of the porosity may result in greatly promoting re-endothelialization.
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http://dx.doi.org/10.1166/jbn.2014.1868DOI Listing
July 2014

Improved biocompatibility of poly(lactic-co-glycolic acid) orv and poly-L-lactic acid blended with nanoparticulate amorphous calcium phosphate in vascular stent applications.

J Biomed Nanotechnol 2014 Jun;10(6):900-10

Biodegradable polymers used as vascular stent coatings and stent platforms encounter a major challenge: biocompatibility in vivo, which plays an important role in in-stent restenosis (ISR). Co-formulating amorphous calcium phosphate (ACP) into poly(lactic-co-glycolic acid) (PLGA) or poly-L-lactic acid (PLLA) was investigated to address the issue. For stent coating applications, metal stents were coated with polyethylene-co-vinyl acetate/poly-n-butyl methacrylate (PEVA/PBMA), PLGA or PLGA/ACP composites, and implanted into rat aortas for one and three months. Comparing with both PEVA/PBMA and PLGA groups after one month, the results showed that stents coated with PLGA/ACP had significantly reduced restenosis (PLGA/ACP vs. PEVA/PBMA vs. PLGA: 21.24 +/- 2.59% vs. 27.54 +/- 1.19% vs. 32.12 +/- 3.93%, P < 0.05), reduced inflammation (1.25 +/- 0.35 vs. 1.77 +/- 0.38 vs. 2.30 +/- 0.21, P < 0.05) and increased speed of re-endothelialization (1.78 +/- 0.46 vs. 1.17 +/- 0.18 vs. 1.20 +/- 0.18, P < 0.05). After three months, the PLGA/ACP group still displayed lower inflammation score (1.33 +/- 0.33 vs. 2.27 +/- 0.55, P < 0.05) and higher endothelial scores (2.33 +/- 0.33 vs. 1.20 +/- 0.18, P < 0.05) as compared with the PEVA/PBMA group. Moreover, for stent platform applications, PLLA/ACP stent tube significantly reduced the inflammatory cells infiltration in the vessel walls of rabbit iliac arteries relative to their PLLA cohort (NF-kappaB-positive cells: 23.31 +/- 2.33/mm2 vs. 9.34 +/- 1.35/mm2, P < 0.05). No systemic biochemical or pathological evidence of toxicity was found in either PLGA/ACP or PLLA/ACP. The co-formulation of ACP into PLGA and PLLA resulted in improved biocompatibility without systemic toxicity.
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http://dx.doi.org/10.1166/jbn.2014.1856DOI Listing
June 2014

Exogenous high-mobility group box 1 protein prevents postinfarction adverse myocardial remodeling through TGF-β/Smad signaling pathway.

J Cell Biochem 2013 Jul;114(7):1634-41

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China.

High-mobility group box 1 (HMGB1) has been reported to attenuate ventricular remodeling, but its mechanism remains mostly unresolved. Transforming growth factor-beta (TGF-β) is a crucial mediator in the pathogenesis of post-infarction remodeling. Our study focused on the effects of HMGB1 on ventricular remodeling, and explored whether or not these effects were depended upon the TGF-β signaling pathway. Rats underwent coronary artery ligation. An intramyocardium injection of phosphate buffered saline (PBS) with or without HMGB1 was administered 3 weeks after myocardial infarction (MI). At 4 weeks after the treatment, HMGB1 significantly increased the left ventricular ejection fraction (LVEF) (P < 0.05), decreased the left ventricular end diastolic dimension (LVEDD; P < 0.05), left ventricular end systolic dimension (LVESD) (P < 0.05) and the infarct size (P < 0.05) compared with control group. The expressions of collagen I, collagen III, and tissue inhibitor of metalloproteinase 2 (TIMP2) were also decreased, while the matrix metalloproteinases 2 (MMP2) and MMP9 expressions were upregulated by HMGB1 injection (P < 0.05) compared with control group. No effect on TIMP3 was observed. Furthermore, TGF-β1 and phosphor-Smad2 (p-Smad2) were significantly suppressed and Smad7 was increased in HMGB1-treated group (P < 0.05) compared with control group, no effects on p-Smad3 and p-p38 were observed. HMGB1 also upregulated Smad 7 expression and decreased the level of collagen I on cardiac fibroblasts (P < 0.05). Silencing of Smad7 gene by small interfering RNA abolished the fibrogenic effects of HMGB1 on cardiac fibroblasts (P < 0.05). These finding suggested that HMGB1 injection modulated ventricular remodeling may function through the possible inhibition of TGF-β/Smad signaling pathway.
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http://dx.doi.org/10.1002/jcb.24505DOI Listing
July 2013