Publications by authors named "Zhizhou Yang"

31 Publications

Xuebijing Protects Against Septic Acute Liver Injury Based on Regulation of GSK-3β Pathway.

Front Pharmacol 2021 30;12:627716. Epub 2021 Apr 30.

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

Xuebijing (XBJ), the only drug approved for the sepsis and multiple organ dysfunction, and its protective effects against acute liver injury (ALI) and its mechanism. The aim of this study was to evaluate the protective effect of XBJ on cecal ligation and perforation (CLP)-induced mouse ALI model and LPS-induced RAW264.7 cell ALI model. Mice were pretreated with XBJ before the CLP model was established, and serum and liver tissues were collected at the end of the experiment to assess the levels of inflammatory factors and liver injury. Results showed that XBJ pretreatment reduced liver/body weight, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in serum, and inhibited levels of pro-inflammatory factors in serum. Cells were treatment with XBJ and modeled by LPS modeling increased cell viability in the XBJ-treated group compared to the model group and XBJ also decreased serum pro-inflammatory factors in a dose-dependent manner. Western blot detected that XBJ also up-regulated the phosphorylated levels of glycogen synthase kinase-3β (p-GSK-3β) and cAMP-response element-binding protein (p-CREB) and down-regulated the phosphorylated level of nuclear factor kappa-B (p-NF-κB) in liver and cell. After overexpression of GSK-3β in cells, the mechanism was further investigated using CO-IP analysis. The binding of p-NF-κB and p-CREB to CREB-binding protein (CBP) was increased and decreased, respectively, indicating that GSK-3β regulated inflammation by regulating the binding of p-NF-κB and p-CREB to CBP. The present studies suggested that the hepatoprotective effect of XBJ may be through up-regulation of GSK-3β (Ser9) and increasing the binding of p-CREB to CBP, thereby alleviating the inflammatory response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.627716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120308PMC
April 2021

One year survival worse for lung retransplants relative to primary lung transplants.

Ann Thorac Surg 2021 May 5. Epub 2021 May 5.

Division of Cardiothoracic Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri.

Background: Outcomes after lung re-transplantation (LRT) remain inferior compared to primary lung transplantation (PLT). We examined the impact of center volume on one-year survival after LRT.

Methods: Using the UNOS database, we abstracted patients undergoing PLT and LRT between January 2006 and December 2017, excluding combined heart-lung transplants and multiple re-transplants. One-year survival after PLT and LRT were compared using propensity score matching. In the LRT cohort, multivariable Cox models with and without time-dependent coefficients were fitted to examine association between transplant center volume and 1-year survival. Center volume was categorized based on inspection of restricted cubic splines.

Results: A total of 20,675 recipients (PLT 19853 [96.0%] vs. LRT 822 [4.0%]) were included. One-year survival was lower for LRT recipients in the matched cohort (PLT 84.8% vs LRT 76.7%). There was steady improvement in one-year survival after LRT (2006-2009 72.1% vs. 2010-2013 76.6% vs. 2014-2017 80.1%). Higher center volume was associated with better 1-year survival after LRT. This survival difference was noted in the initial 30 days after transplantation (Intermediate vs. Low volume, HR 0.282 [0.151-0.526]; High vs. Low volume HR 0.406 [0.224-0.737]) but became insignificant after 30 days.

Conclusions: Superior 1-year survival after LRT at higher volume centers is predominantly due to better 30-day outcomes. This finding suggests that LRT candidates may be referred to higher volume centers for surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.athoracsur.2021.03.112DOI Listing
May 2021

Ferulic acid positively modulates the inflammatory response to septic liver injury through the GSK-3β/NF-κB/CREB pathway.

Life Sci 2021 May 4;277:119584. Epub 2021 May 4.

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China. Electronic address:

Aims: Ferulic acid (FA) is a component found in plants that has free radical scavenging and liver-protective properties. Acute liver injury (ALI) is a serious complication of sepsis and is closely associated with changes in the levels of inflammatory factors. This study was taken to examine the role of FA in cecal ligation and perforation (CLP)-induced murine ALI and lipopolysaccharide (LPS)-induced cellular ALI models.

Materials And Methods: An in vivo ALI model was established by performing CLP surgery on C57BL/6 mice. After the ALI model was established, mice were examined for liver injury, including HE staining to observe tissue sections, the percentage of liver/body weight and inflammatory factor levels. Myeloperoxidase (MPO), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured in liver or serum using commercial kits. An in vitro ALI model was established using LPS-stimulated RAW264.7 cells. Cell viability was measured by MTT method and the intracellular levels of IL-10, IL-1β, IL-6, IL-12 and TNF-α inflammatory factors were measured using kits. The expression of GSK-3β, NF-κB and CREB was measured by western blot or immunofluorescence.

Key Findings: FA pretreatment significantly reduced liver/body weight ratio, decreased MPO, AST and ALT activity, alleviated the inflammatory responses and improved CLP-induced histopathological changes in liver. In addition, in vitro results showed that FA could dose-dependently increase the viability of RAW264.7 cells and decrease the levels of pro-inflammatory factors.

Significance: In conclusion, our data suggest that FA can ameliorate ALI-induced inflammation via the GSK-3β/NF-κB/CREB pathway, suggesting that FA can be used to protect the liver against ALI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2021.119584DOI Listing
May 2021

The Impact of Center Volume on Outcomes in Lung Transplantation.

Ann Thorac Surg 2021 Apr 12. Epub 2021 Apr 12.

Washington University School of Medicine, Division of Cardiothoracic Surgery. Electronic address:

Background: Studies in lung transplantation have shown variable association between hospital volume and clinical outcomes. We aimed to identify the pattern of effect of hospital volume on individual survival after lung transplantation.

Methods: We performed a retrospective analysis using the United Network for Organ Sharing national thoracic organ transplantation database. Adult patients who underwent lung transplantation between January 2013 and December 2017 were included. The association between mean annual center volume and 1-year overall survival was examined using restricted cubic splines in a random-effect multivariable Cox model. The volume threshold for optimal 1-year overall survival was subsequently approximated via the maximum likelihood approach using segmented linear splines in the same model.

Results: The study included 10,007 patients at 71 transplant centers. Median annual center volume was 22.0 cases (IQR 10.6-38.0 cases). A center volume threshold was identified at 33 cases/year (95% CI 28-37 cases). Higher center volume up to 33 cases/year was associated with better 1-year survival (HR = 0.989, 95% CI 0.980 - 0.999 every additional case). Further increase in center volume above 33 cases/year showed no additional benefit (HR = 1.000, 95% CI 0.996 - 1.003 every additional case). Twenty-three centers (32.4%) reached the volume threshold of 33 cases/year.

Conclusions: One-year survival after lung transplantation improved with increasing center volume up to 33 cases/year. Low volume centers below the 33 cases/year threshold had large variations in their outcomes and had a higher risk of performing poorly, though many of them maintained good performance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.athoracsur.2021.03.092DOI Listing
April 2021

Different-team procurements: A potential solution for the unintended consequences of change in lung allocation policy.

Am J Transplant 2021 Feb 27. Epub 2021 Feb 27.

Department of Surgery, Division of Cardiothoracic Surgery, Washington University, St. Louis, MO.

The new lung allocation policy has led to an increase in distant donors and consequently enhanced logistical burden of procuring organs. Though early single-center studies noted similar outcomes between same-team transplantation (ST, procuring team from transplanting center) and different-team transplantation (DT, procuring team from different center), the efficacy of DT in the contemporary era remains unclear. In this study, we evaluated the trend of DT, rate of transplanting both donor lungs, 1-year graft survival, and risk of Grade 3 primary graft dysfunction (PGD) using the Scientific Registry of Transplant Recipient (SRTR) database from 2006 to 2018. A total of 21619 patients (DT 2085, 9.7%) with 19837 donors were included. Utilization of DT decreased from 15.9% in 2006 to 8.5% in 2018. Proportions of two-lung donors were similar between the groups, and DT had similar 1-year graft survival as ST for both double (DT, HR 1.108, 95% CI 0.894-1.374) and single lung transplants (DT, HR 1.094, 95% CI 0.931-1.286). Risk of Grade 3 PGD was also similar between ST and DT. Given our results, expanding DT may be a feasible option for improving lung procurement efficiency in the current era, particularly in light of the COVID-19 pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.16553DOI Listing
February 2021

Arctigenin Suppressed Epithelial-Mesenchymal Transition Through Wnt3a/β-Catenin Pathway in PQ-Induced Pulmonary Fibrosis.

Front Pharmacol 2020 16;11:584098. Epub 2020 Dec 16.

Department of Emergency Medicine, Jinling Clinical College of Nanjing Medical University, Nanjing, China.

Arctigenin (ATG), a major bioactive substance of Fructus Arctii, counters renal fibrosis; however, whether it protects against paraquat (PQ)-induced lung fibrosis remains unknown. The present study was to determine the effect of ATG on PQ-induced lung fibrosis in a mouse model and the underlying mechanism. Firstly, we found that ATG suppressed PQ-induced pulmonary fibrosis by blocking the epithelial-mesenchymal transition (EMT). ATG reduced the expressions of Vimentin and α-SMA (lung fibrosis markers) induced by PQ and restored the expressions of E-cadherin and Occludin (two epithelial markers) and . Besides, the Wnt3a/β-catenin signaling pathway was significantly activated in PQ induced pulmonary fibrosis. Further analysis showed that pretreatment of ATG profoundly abrogated PQ-induced EMT-like phenotypes and behaviors in A549 cells. The Wnt3a/β-catenin signaling pathway was repressed by ATG treatment. The overexpression of Wnt3a could weaken the therapeutic effect of ATG in A549 cells. These findings suggested that ATG could serve as a new therapeutic candidate to inhibit or even reverse EMT-like changes in alveolar type II cells during PQ-induced lung fibrosis, and unraveled that the Wnt3a/β-catenin pathway might be a mechanistic tool for ATG to control pulmonary fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.584098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772408PMC
December 2020

Regionalization for thoracic surgery: Economic implications of regionalization in the United States.

J Thorac Cardiovasc Surg 2021 May 19;161(5):1705-1709. Epub 2020 Nov 19.

Division of Cardiothoracic Surgery, Washington University School of Medicine, St Louis, Mo.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtcvs.2020.10.132DOI Listing
May 2021

Impact of Nighttime Lung Transplantation on Outcomes and Costs.

Ann Thorac Surg 2020 Oct 13. Epub 2020 Oct 13.

Department of Surgery, Division of Cardiothoracic Surgery, Washington University, St Louis, Missouri. Electronic address:

Background: Previous studies in the field of organ transplantation have shown a possible association between nighttime surgery and adverse outcomes. We aim to determine the impact of nighttime lung transplantation on postoperative outcomes, long-term survival, and overall cost.

Methods: We performed a single-center retrospective cohort analysis of adult lung transplant recipients who underwent transplantation between January 2006 and December 2017. Data were extracted from our institutional Lung Transplant Registry and Mid-America Transplant services database. Patients were classified into 2 strata, daytime (5 AM to 6 PM) and nighttime (6 PM to 5 AM), based on time of incision. Major postoperative adverse events, 5-year overall survival, and 5-year bronchiolitis obliterans syndrome-free survival were examined after propensity score matching. Additionally we compared overall cost of transplantation between nighttime and daytime groups.

Results: Of the 740 patients included in this study, 549 (74.2%) underwent daytime transplantation and 191 (25.8%) underwent nighttime transplantation (NT). Propensity score matching yielded 187 matched pairs. NT was associated with a higher risk of having any major postoperative adverse event (adjusted odds ratio, 1.731; 95% confidence interval, 1.093-2.741; P = .019), decreased 5-year overall survival (adjusted hazard ratio, 1.798; 95% confidence interval, 1.079-2.995; P = .024), and decreased 5-year bronchiolitis obliterans syndrome-free survival (adjusted hazard ratio, 1.556; 95% confidence interval, 1.098-2.205; P = .013) in doubly robust multivariable analyses after propensity score matching. Overall cost for NT and daytime transplantation was similar.

Conclusions: NT was associated with a higher risk of major postoperative adverse events, decreased 5-year overall survival, and decreased 5-year bronchiolitis obliterans syndrome-free survival. Our findings suggest potential benefits of delaying NT to daytime transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.athoracsur.2020.07.060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041913PMC
October 2020

Study on the Synthesis and Thermal Stability of Silicone Resin Containing Trifluorovinyl Ether Groups.

Polymers (Basel) 2020 Oct 5;12(10). Epub 2020 Oct 5.

School of Materials Science and Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.

Silicone resin is a high-temperature resistant material with excellent performance. The improvement of its thermal stability has always been the pursuit of researchers. In this paper, a sequence of silicone resins containing trifluorovinyl ether groups were prepared by the co-hydrolysis-polycondensation of methyl alkoxysilane monomers and {4-[trifluorovinyl(oxygen)]phenyl}methyldiethoxysilane. The structures of the silicone resins were characterized by FT-IR and H NMR. The curing process of them was studied by DSC and FT-IR spectra, and results showed that the curing of the resins included the condensation of the Si-OH groups and the [2 + 2] cyclodimerization reaction of the TFVE groups, which converted to perfluorocyclobutane structure after curing. The thermal stability and thermal degradation behavior of them was studied by TGA and FT-IR spectra. Compared with the pure methyl silicone resin, silicone resins containing TFVE groups showed better thermal stability under both N and air atmosphere. Their hydrophobic properties were characterized by contact angle test. Results showed that PFCB structure also improved the hydrophobicity of the silicone resin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/polym12102284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601899PMC
October 2020

Local versus distant lung donor procurement does not influence short-term clinical outcomes.

J Thorac Cardiovasc Surg 2020 Aug 27. Epub 2020 Aug 27.

Division of Cardiothoracic Surgery, Department of Surgery, Washington University, St Louis, Mo.

Objective: The purpose of this study was to recognize clinically meaningful differences in lung transplant outcomes based on local or distant lung procurement. This could identify if the lung allocation policy change would influence patient outcomes.

Methods: This single-center retrospective cohort study analyzed adult patients who underwent lung transplant from 2006 to 2017. Donor and recipient data were abstracted from a collaborative, prospective registry shared by our local organ procurement organization, and tertiary medical center. Short-term outcomes, 1-year survival, and hospitalization costs were compared between local and distant lung transplants defined by donor service area.

Results: Of the 722 lung transplants performed, 392 (54%) had local donors and 330 (46%) had distant donors. Donors were similar in age and cause of death. Recipients were significantly different in diagnosis and local recipients had lower median lung allocation scores (local, 37.3 and distant, 44.9; P < .01). Distant lung transplants had longer total ischemic times (local, 231 ± 52 minutes and distant, 313 ± 48 minutes; P < .01). The rate of major complications, length of hospital stay, and 1-year survival were similar between groups. Distant lung transplants were associated with higher median overall cost (local, $183,542 and distant, $229,871; P < .01). Local lung transplants were more likely to be performed during daytime (local, 333 out of 392 [85%] and distant, 291 out of 330 [61%]; P < .01).

Conclusions: Local lung transplants are associated with shorter ischemic times, lower cost, and greater likelihood of daytime surgery. Short- and intermediate-term outcomes are similar for lung transplants from local and distant donors. The new lung allocation policy, with higher proportion of distant lung transplants, is likely to incur greater costs but provide similar outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtcvs.2020.07.115DOI Listing
August 2020

Long non-coding RNA Hsp4 alleviates lipopolysaccharide-induced apoptosis of lung epithelial cells via miRNA-466m-3p/DNAjb6 axis.

Exp Mol Pathol 2020 12 23;117:104547. Epub 2020 Sep 23.

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China. Electronic address:

Acute lung injury (ALI), as a life-threatening syndrome, is mainly characterized with diffuse alveolar injury, excessive pulmonary inflammation, edema and apoptosis of lung epithelial cells. This study investigated the effects of LncRNA Hsp4 (Hsp4, ENSMUST00000175718) on lipopolysaccharide (LPS)-induced apoptosis of MLE-12 cells. In our research, we found that LPS treatment remarkably induced apoptosis of MLE-12 cells and decreased the expression of Hsp4. Overexpression of Hsp4 significantly reversed LPS-induced cell apoptosis through inhibiting mTOR signaling, while suppression of Hsp4 presented opposite effects. Further results showed that Hsp4 positively regulated the expression of miR-466m-3p. Knockdown of miR-466m-3p reversed LPS-induced cell apoptosis via increasing the levels of DNAjb6 which was confirmed to be the target gene of miR-466m-3p. This finding will be helpful for further understanding the critical roles of Hsp4 in ALI and may provide potential targets for ALI diagnosis and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yexmp.2020.104547DOI Listing
December 2020

Paraquat induces pulmonary fibrosis through Wnt/β-catenin signaling pathway and myofibroblast differentiation.

Toxicol Lett 2020 Oct 11;333:170-183. Epub 2020 Aug 11.

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, PR China; Department of Emergency Medicine, Jinling Hospital, Southern Medical University, Nanjing, 210002, PR China. Electronic address:

Paraquat (PQ) poisoning-induced pulmonary fibrosis always results in fatal harm to patients. Our study aimed to investigate the functions of the Wnt/β-catenin pathway in PQ-induced pulmonary fibrosis. By comparing the proteomic profiles of rat lung tissues using protein array in the absence or presence of PQ, the Wnt/β-catenin signaling, as a fibrosis-related pathway, was discovered to be profoundly activated by PQ. The protein levels of Wnt/β-catenin signaling components including MMP-2, β-catenin, Wnt3a, Wnt10b, Cyclin D1, and WISP1 were increased in PQ-treated rat lung tissues. Surprisingly, PQ was found to be able to promote lung epithelial cells and fibroblasts differentiating into myofibroblasts by activating Wnt/β-catenin signaling pathway. Dickkopf-1 (DKK1), an antagonist of Wnt/β-catenin signaling pathway, could inhibit the myofibroblast differentiation and attenuate PQ-induced pulmonary fibrogenesis in vitro and in vivo. The expression levels of fibroblasts markers Vimentin, α-smooth muscle actin (α-SMA) and Collagen I was detected and found to be increased when PQ treated and restored with additional DKK1 treatment. In summary, these assays indicated that Wnt/β-catenin signaling pathway played a regulatory role in the differentiation of lung epithelial cells and fibroblasts, and the pathogenesis of pulmonary fibrosis related to PQ. Inhibition of the Wnt/β-catenin signaling pathway may be investigated further as a potential fibrosis suppressor for pulmonary fibrosis therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxlet.2020.08.004DOI Listing
October 2020

Shipping Lungs Greater Distances Increases Costs Without Cutting Waitlist Mortality.

Ann Thorac Surg 2020 11 6;110(5):1691-1697. Epub 2020 Jun 6.

Division of Cardiothoracic Surgery, Department of Surgery, Washington University, St Louis, Missouri. Electronic address:

Background: On November 24, 2017, a change in lung allocation policy was initiated to replace the donor service area with a 250-nautical-mile radius circle around the donor hospital. We aim to analyze the consequences of this change, including organ acquisition cost and transplant outcomes, at the national level.

Methods: Data on adult patients undergoing lung transplantation between April 27, 2017, and June 22, 2018 (30 weeks before to 30 weeks after allocation policy change) were extracted from the Scientific Registry of Transplant Recipients database. Patients were classified into pre-change and post-change subgroups. Six-month overall survival was evaluated by Kaplan-Meier analysis. Organ acquisition costs were compared between the pre-change and post-change groups.

Results: Of the 3317 adult patients removed from the waiting list during the study period (pre-change 1637 vs post-change 1680), 2734 underwent transplantation (pre-change 1371 of 1637 [83.8%] vs post-change 1363 of 1680 [81.1%]), and 382 died or became too sick to be transplanted (pre-change 168 of 1637 [10.3%] vs post-change 214 of 1680 [12.7%], P = .077). Six-month survival rates of transplanted patients were similar between the two groups. However, average organ acquisition costs increased after policy change (pre-change $50,735 ± $10,858 vs post-change $53,440 ± $10,247, P < .001) with an increase in nonlocal donors (pre-change 44.3% vs post-change 68.9%, P < .001).

Conclusions: Organ acquisition costs and resource utilization increased with the new lung allocation policy, whereas deaths on the waiting list or after transplantation did not decrease. Further optimization of the allocation policy is necessary to balance access to transplant and proper stewardship of human and financial resources.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.athoracsur.2020.04.086DOI Listing
November 2020

Schizandrin B Mitigates Rifampicin-Induced Liver Injury by Inhibiting Endoplasmic Reticulum Stress.

Biol Pharm Bull 2020 Jan 30;43(1):145-152. Epub 2019 Oct 30.

Nanjing University of Chinese Medicine.

Schisandra chinensis is widely used and effective in protecting liver. There are many mechanisms of drug-induced hepatocyte injury, among which endoplasmic reticulum (ER) stress-induced cell injury plays an important role. However, little is known about whether schisandra chinensis can inhibit rifampicin (RFP)-induced hepatocyte injury by affecting ER stress. In our study, firstly, L02 cells were treated with different concentrations of RFP for different time intervals, and the apoptosis, survival rate and endoplasmic reticulum stress gene and protein expressions of glucose-regulated protein 78 (GRP 78), PKR-like ER kinase (PERK), activating transcription factor (ATF)4, C/EBP-homologus protein (CHOP), ATF6, arginine-rich, mutated in early stage tumors (ARMET), p-inositol-requiring enzyme 1 (IRE1) and X-box binding protein 1 (XBP-1) were measured. We found that RFP increased apoptosis of L02 cells, decreased cell survival, and increased the gene and protein expression levels of GRP78, PERK, ATF4, CHOP, ATF6, ARMET, p-IRE1 and XBP-1, suggesting that RFP could induce hepatocyte injury, and the degree of injury was positively correlated with the dose and time of RFP. Next, we treated RFP-damaged hepatocytes with schizandrin B. We found that schizandrin B increased cell survival rate in dose-dependent and time-dependent manner, decreased cell apoptosis rate, and reduced protein and gene expression levels of GRP78, PERK, ATF4, CHOP, ATF6, ARMET and XBP-1. These results indicate that schizandrin B alleviates RFP-induced injury in L02 cells by inhibiting ER stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1248/bpb.b19-00725DOI Listing
January 2020

Curcumin relieves paraquat‑induced lung injury through inhibiting the thioredoxin interacting protein/NLR pyrin domain containing 3‑mediated inflammatory pathway.

Mol Med Rep 2019 Dec 23;20(6):5032-5040. Epub 2019 Aug 23.

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.

When paraquat (PQ) enters the human body, it increases oxidative stress and inflammation, ultimately resulting in acute lung injury (ALI). Curcumin, a naturally occurring compound, has been reported to ameliorate PQ‑induced ALI; however, the underlying molecular mechanisms remain unclear. In the present study, normal lung fibroblasts (WI‑38VA13) were treated with 10 µmol/l PQ for 48 h, followed by a further 48 h incubation with 300 µmol/l curcumin. Cells were then harvested to determine their viability. Flow cytometry was performed to analyze the levels of reactive oxygen species (ROS) and the rate of apoptosis. The levels of apoptotic proteins and activation of the thioredoxin interacting protein/NLR pyrin domain containing 3 (TXNIP/NLRP3) axis were measured via reverse transcription‑quantitative polymerase chain reaction and western blot analyses. Proinflammatory cytokine levels were examined using enzyme‑linked immunosorbent assays. Finally, the expression levels of Notch1, extracellular signal‑regulated kinase 1/2 (ERK1/2) and phosphorylated‑ERK1/2 were evaluated via western blotting. Following treatment with curcumin, PQ‑induced increases in ROS levels and apoptosis were significantly attenuated, and Bcl‑2 expression levels were upregulated, whereas those of Bax were downregulated. It was also observed that curcumin treatment downregulated the expression levels of TXNIP, NLRP3, interleukin (IL)‑1β and IL‑18, and downstream caspase‑1 compared with PQ treatment alone. Curcumin significantly attenuated the upregulation of Notch1 without affecting ERK1/2 phosphorylation. The present findings suggested that the inhibitory effects of curcumin on TXINP1 may inhibit activation of the NLRP3 inflammasome, subsequently suppressing the upregulation of proinflammatory cytokines and ultimately improving PQ‑induced ALI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2019.10612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854544PMC
December 2019

Advances in nanomaterials for use in photothermal and photodynamic therapeutics (Review).

Mol Med Rep 2019 Jul 9;20(1):5-15. Epub 2019 May 9.

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.

Nanomaterials play crucial roles in the diagnosis and treatment of diseases. Photothermal and photodynamic therapy, as two minimally invasive therapeutic methods, have promising potential in the diagnosis and prevention of cancer. Recently, many photothermal materials (such as noble metal material, transition metal sulfur oxides, carbon material and upconversion nanomaterial) and photodynamic materials (such as phthalein cyanogen, porphyrins and other dye molecules) have been applied in photothermal therapy (PTT) and photodynamic therapy (PDT). Moreover, as nanomaterials have suitable biocompatibility, these materials have been applied in cancer therapy. In the present review, we summarized the effects of different material types, synthesis methods, material morphologies and surface modifications on the outcomes of cancer therapy. The application of nanomaterials in PTT and PDT was introduced and the advantages and disadvantages of PTT and PDT in the prevention of cancer were discussed. Finally, we discussed the application of nanomaterials in the combination of PTT and PDT in cancer treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2019.10218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579972PMC
July 2019

Retrospective study of clinical features and prognosis of edaravone in the treatment of paraquat poisoning.

Medicine (Baltimore) 2019 May;98(19):e15441

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China.

To observe whether edaravone can protect organs and inhibit pulmonary fibrosis in patients with paraquat poisoning and to provide a method for clinical intervention for paraquat poisoning.Forty-four cases of paraquat poisoning were collected from March 2011 to December 2017 in our hospital. Eighteen cases from March 2011 to November 2013 did not receive edaravone treatment and were considered the control group, and 26 cases from January 2014 to December 2017 were treated with edaravone and were considered the observation group. Injuries to the central nervous system, heart, liver, kidney, and digestive system were evaluated on at 24 hours, 3 days, and 7 days after hospitalization. The expression of serum inflammatory factors (interleukin [IL]-6, IL-10, tumor necrosis factor-α [TNF-α]) and oxidative stress correlation (superoxide dismutase [SOD] and malondialdehyde [MDA]) were assayed at 24 hours, 3 days, and 7 days after being hospitalized. After 7, 14, and 30 days, the changes in pathological lung characteristics in the 2 groups were assessed, and survival rates were calculated.Edaravone significantly increased the serum levels of SOD and obviously markedly reduce the serum levels of IL-6, IL-10, TNF-α, and MDA in patients poisoned with paraquat (P < .05). Edaravone significantly protected the liver (P = .021), cardiovascular (P = .031), and renal (P = .028) organs of patients from paraquat poisoning-induced injury after 7 days but had no significant protection or improvement on respiratory and digestive tract damage. Edaravone delayed the occurrence of pulmonary fibrosis and increase the survival time of patients at 7 and 14 days (P < .05). However, the 1-month follow-up found that edaravone did not reduce pulmonary fibrosis (77.8% vs 73.1%, P = .615) and did not increase the survival rate of the patients (61.1% vs 65.3%, P = .853).Edaravone is beneficial for protecting the kidneys and liver from paraquat poisoning through reducing oxidative stress and inhibiting inflammatory response. It can also inhibit the pulmonary fibrosis process and prolong the survival time of the patients. However, no significant improvements were seen in the probability of pulmonary fibrosis and the survival rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000015441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531030PMC
May 2019

Investigation on the Properties of PMMA/Reactive Halloysite Nanocomposites Based on Halloysite with Double Bonds.

Polymers (Basel) 2018 Aug 15;10(8). Epub 2018 Aug 15.

Shandong Provincial Key Laboratory of Processing and Testing Technology of Glass & Functional Ceramics, School of Material Science and Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.

PMMA/reactive halloysite nanocomposites were firstly prepared using reactive halloysite with double bonds. The halloysite was functionalized to improve its dispersion in the polymer matrix. The reactive halloysite could increase the molecular weight of PMMA. The molecular distribution of PMMA/reactive halloysite nanocomposite was more uniform than that of PMMA. The moisture absorption of PMMA/reactive halloysite nanocomposite increased with the addition of the reactive halloysite. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) confirmed that the thermal stability of PMMA/reactive halloysite nanocomposites was greatly enhanced. Significant improvement in the mechanical property of PMMA nanocomposites was achieved by the addition of 3 wt % reactive halloysite. A 31.1% increase in tensile strength and a 64.2% increase in Young' modulus of the nanocomposites with 3 wt % of the reactive halloysite were achieved. Finally, the formation mechanism of PMMA/reactive halloysites nanocomposites was proposed. This approach demonstrated the potential for general applicability to other polymer nanocomposites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/polym10080919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403715PMC
August 2018

E3 ubiquitin ligase tripartite motif 7 positively regulates the TLR4-mediated immune response via its E3 ligase domain in macrophages.

Mol Immunol 2019 05 28;109:126-133. Epub 2019 Mar 28.

Department of Emergency Medicine, Jinling Clinical Medical College of Nanjing Medical University, Nanjing, China; Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. Electronic address:

Members of the tripartite motif (TRIM) family as E3 ubiquitin ligases have been regarded as critical regulators of innate immunity and antiviral response. However, the role of TRIM7 is still elusive. Here, we provide evidence for the importance of TRIM7 in regulation of the TLR4-mediated innate response. In detail, we find that TRIM7 is highly expressed in antigen-presenting cells like macrophages. Knockdown of TRIM7 clearly inhibits the LPS-induced production of IFN-β, TNF-α and IL-6 in macrophages. Conversely, forced expression of TRIM7 could exert an opposite effect on these pro-inflammatory cytokines. Further analysis indicates that such effect is mediated by the TLR4-associated signaling pathways including MAPKs, NF-κB and IRF3-involved pathways. Truncation of the E3 ligase domain on TRIM7 may reduce the production of pro-inflammatory cytokines, suggesting a critical role of this domain in the regulation of LPS-initiated innate response. Taken together, we report here that TRIM7 may facilitate the TLR4-mediated innate response via its E3 ligase domain in macrophages, which provides new insight into the mechanistic role of TRIM7 in innate immunity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molimm.2019.01.015DOI Listing
May 2019

A Chemical Inhibitor of Cell Growth Reduces Cell Size in Bacillus subtilis.

ACS Chem Biol 2019 04 18;14(4):688-695. Epub 2019 Mar 18.

Department of Biochemistry , University of Toronto , Toronto , Ontario M5S 1A8 , Canada.

Bacteria exhibit complex responses to biologically active small molecules. These responses include reductions in transcriptional and translational efficiency, alterations in metabolic flux, and in some cases, dramatic changes in growth and morphology. Here, we describe Min-1, a novel small molecule that inhibits growth of Gram-positive bacteria by targeting the cell envelope. Subinhibitory levels of Min-1 inhibits sporulation in Streptomyces venezuelae and reduces growth rate and cell length in Bacillus subtilis. The effect of Min-1 on B. subtilis cell length is significant at high growth rates sustained by nutrient-rich media but drops off when growth rate is reduced during growth on less energy-rich carbon sources. In each medium, Min-1 has no impact on the proportion of cells containing FtsZ-rings, suggesting that Min-1 reduces the mass at which FtsZ assembly is initiated. The effect of Min-1 on size is independent of UDP-glucose, which couples cell division to carbon availability, and the alarmone ppGpp, which reduces cell size via its impact on fatty acid synthesis. Min-1 activates the LiaRS stress response, which is sensitive to disruptions in the lipid II cycle and the cell membrane, and also compromises cell membrane integrity. Therefore, this novel synthetic molecule inhibits growth at high concentrations and induces a short-cell phenotype at subinhibitory concentrations that is independent of known systems that influence cell length, highlighting the complex interactions between small molecules and cell morphology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acschembio.8b01066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474795PMC
April 2019

Protective effect of ginsenoside Rg1 on LPS-induced apoptosis of lung epithelial cells.

Mol Immunol 2018 Nov 22. Epub 2018 Nov 22.

Department of Emergency Medicine, Jinling Clinical Medical College of Nanjing Medical University, Nanjing, 210002, PR China; Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, PR China. Electronic address:

Sepsis-induced acute lung injury (ALI) is a life-threatening medical condition with high mortality and morbidity in the critical care units. Though, it was commonly accepted that inflammation and apoptosis of lung epithelial cells played an essential role in the pathogenesis of ALI, the underlying mechanism remain unknown. In our study, we found that LPS-induced cell apoptosis could be counteracted by elevated cell autophagy. In LPS-treated MLE-12 cells, suppression of autophagy via 3-MA could aggravate LPS-induced apoptosis, while activation of autophagy via Rapamycin could effectively impair the apoptosis of MLE-12 cells induced by LPS. In order to further discover the molecular regulation mechanism between apoptosis and autophagy in LPS-treated MLE-12 cells, we demonstrated that autophagy could induced the expression of Nrf2, followed with the decrease of p-p65. Targeted inhibition of Nrf2 could induce enlarged cell apoptosis via increasing the level of p-p65. In addition, we demonstrated that ginsenoside Rg1 protected MLE-12 cells from LPS-induced apoptosis via augmenting autophagy and inducing the expression of Nrf2. Our data implicates that activation of autophagy and Nrf2 by ginsenoside Rg1 may provide a preventive and therapeutic strategy for ALI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molimm.2018.11.003DOI Listing
November 2018

Fatty Acid Availability Sets Cell Envelope Capacity and Dictates Microbial Cell Size.

Curr Biol 2017 Jun 8;27(12):1757-1767.e5. Epub 2017 Jun 8.

Department of Biology, Washington University in St. Louis, St. Louis, MO 63130, USA. Electronic address:

Nutrients-and by extension biosynthetic capacity-positively impact cell size in organisms throughout the tree of life. In bacteria, cell size is reduced 3-fold in response to nutrient starvation or accumulation of the alarmone ppGpp, a global inhibitor of biosynthesis. However, whether biosynthetic capacity as a whole determines cell size or whether particular anabolic pathways are more important than others remains an open question. Here we identify fatty acid synthesis as the primary biosynthetic determinant of Escherichia coli size and present evidence supporting a similar role for fatty acids as a positive determinant of size in the Gram-positive bacterium Bacillus subtilis and the single-celled eukaryote Saccharomyces cerevisiae. Altering fatty acid synthesis recapitulated the impact of altering nutrients on cell size and morphology, whereas defects in other biosynthetic pathways had either a negligible or fatty-acid-dependent effect on size. Together, our findings support a novel "outside-in" model in which fatty acid availability sets cell envelope capacity, which in turn dictates cell size. In the absence of ppGpp, limiting fatty acid synthesis leads to cell lysis, supporting a role for ppGpp as a linchpin linking expansion of cytoplasmic volume to the growth of the cell envelope to preserve cellular integrity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cub.2017.05.076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551417PMC
June 2017

[A Meta analysis on the associations between air pollution and respiratory mortality in China].

Zhonghua Liu Xing Bing Xue Za Zhi 2015 Aug;36(8):889-95

Department of Emergency Medicine, Nanjing General Hospital of Nanjing Military Command, Nanjing 210002, China; Email:

Objective: To analyze the associations between air pollution and adverse health outcomes on respiratory diseases and to estimate the short-term effects of air pollutions [Particulate matter with particle size below 10 microns (PM(10)), PM(10) particulate matter with particle size below 2.5 microns (PM(2.5)), nitrogen dioxide (NO₂), sulphur dioxide (SO₂) and ozone (O₃)] on respiratory mortality in China.

Methods: Data related to the epidemiological studies on the associations between air pollution and adverse health outcomes of respiratory diseases that published from 1989 through 2014 in China, were collected by systematically searching databases of PubMed, SpringerLink, Embase, Medline, CNKI, CBM and VIP in different provinces of China. Short-term effects between (PM(10), PM(2.5), NO₂, SO₂, O₃) and respiratory mortality were analyzed by Meta-analysis method, and estimations were pooled by random or fixed effect models, using the Stata 12.0 software.

Results: A total of 157 papers related to the associations between air pollution and adverse health outcomes of respiratory diseases in China were published, which covered 79.4% of all the provinces in China. Results from the Meta-analysis showed that a 10 µg/m³ increase in PM10, PM(2.5), NO₂, SO₂, and O₃was associated with mortality rates as 0.50% (95% CI: 0-0.90%), 0.50% (95% CI: 0.30%-0.70%), 1.39% (95% CI: 0.90%-1.78%), 1.00% (95% CI: 0.40%-1.59%) and 0.10% (95% CI: -1.21%-1.39%) in respiratory tracts, respectively. No publication bias was found among these studies.

Conclusion: There seemed positive associations existed between PM(10)/PM(2.5)/NO₂/SO₂and respiratory mortality in China that the relationship called for further attention on air pollution and adverse health outcomes of the respiratory diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
August 2015

Recent Advances in Discovering the Role of CCL5 in Metastatic Breast Cancer.

Mini Rev Med Chem 2015 ;15(13):1063-72

Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Ave., 77030 Houston, TX, USA.

A variety of therapeutic strategies are currently under investigation to inhibit factors that promote tumor invasion, as metastasis is the most common cause of mortality for cancer patients. Notably, considerable emphasis has been placed on studying metastasis as a dynamic process that is highly dependent on the tumor microenvironment. In regards to breast cancer, chemokine C-C motif ligand 5 (CCL5), which is produced by tumor-associated stromal cells, has been established as an important contributor to metastatic disease. This review summarizes recent discoveries uncovering the role of this chemokine in breast cancer metastasis, including conditions that increase the generation of CCL5 and effects induced by this signaling pathway. In particular, CCL-5-mediated cancer cell migration and invasion are discussed in the context of intertwined feedback loops between breast cancer cells and stromal cells. Moreover, the potential use of CCL5 and its receptor chemokine C-C motif receptor 5 (CCR5) as targets for preventing breast cancer metastasis is also reviewed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4968951PMC
http://dx.doi.org/10.2174/138955751513150923094709DOI Listing
June 2016

Chitosan layered gold nanorods as synergistic therapeutics for photothermal ablation and gene silencing in triple-negative breast cancer.

Acta Biomater 2015 Oct 17;25:194-204. Epub 2015 Jul 17.

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China. Electronic address:

Unlabelled: Small interfering RNAs (siRNAs) are extensively studied due to their promising potential as therapeutic agents for a wide variety of diseases, including cancer. However, efficient delivery of siRNAs to target cells and tissues is problematic due to a lack of suitable delivery vehicles. In this work, we developed a layer-by-layer assembled chitosan-gold nanorods (Chit-Au NRs) siRNA delivery system to overcome biological barriers upon systemic injection. This platform was able to protect siRNAs form degradation upon exposure to ribonuclease (RNase) or serum. Confocal and intravital microscopy reveals that Chit-Au NRs/siRNAs are successfully delivered into target cells and tissue, and can efficiently escape from endosomal/lysosomal structures. Furthermore, Chit-Au NRs/siRNA were found to accumulate in high levels in tumor tissue. The delivery system was able to inhibit the oncogene expression (pyruvate kinase isozymeM2, PKM2) in MDA-MB-231 triple negative breast cancer cells, resulting in suppression of cell proliferation and migration. Moreover, the anticancer efficacy was further enhanced through NR-mediated photothermal ablation. In conclusion, the synergistic therapeutic properties of Chit-Au NRs/siRNA enable effective suppression of cancer growth.

Statement Of Significance: Small interfering RNA (siRNA) therapy has promising therapeutic applications, since the expression of any protein can be suppressed. However the successful implementation of siRNA has been challenging, due to rapid degradation, poor intracellular uptake and insufficient endosomal escape. Here, we have developed a gold nanorod/chitosan-based delivery vehicle for siRNA therapy. This platform successfully overcomes the afore-mentioned challenges and can simultaneously be used for photothermal therapy, due to the optical properties of gold nanorods. We show that the anticancer activity is dramatically improved by combining thermal therapy with gene silencing. Furthermore, the Au NRs carrier shows high accumulation in tumor tissue and high transfection efficiency. This manuscript has been reviewed and approved by all co-authors. The research has not been disclosed or published and is not under consideration for publication elsewhere. We would appreciate if the manuscript could be reviewed and considered for publication in Acta BIOMATERIALIA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actbio.2015.07.026DOI Listing
October 2015

Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

Mol Med Rep 2015 Jul 24;12(1):1091-7. Epub 2015 Mar 24.

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China.

It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2015.3537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4438944PMC
July 2015

Protective effects of intestinal trefoil factor (ITF) on gastric mucosal epithelium through activation of extracellular signal-regulated kinase 1/2 (ERK1/2).

Mol Cell Biochem 2015 Jun 17;404(1-2):263-70. Epub 2015 Mar 17.

Department of Emergency, Jinling Hospital, Medical School of Nanjing University, Zhongshan East Road 305, Nanjing, 210002, People's Republic of China.

The rapid repair of gastric mucosa is critical upon exposure to injurious agents. Intestinal trefoil factor (ITF) is a member of the trefoil factor family domain peptides, which play an important role in the cytoprotection of gastric epithelium. However, the underlying molecular mechanisms that are responsible for ITF-induced gastric epithelial repair remain unclear. In the present study, we demonstrate that ITF enhances the proliferation and migration of GES-1 gastric endothelial cells in a dose- and time-dependent manner through the activation of extracellular signal-regulated kinase 1/2 (ERK1/2). Furthermore, the ITF-mediated protection of GES-1 cells from a NS398 (nonsteroidal anti-inflammatory drug) was dependent on the ERK1/2 signaling pathway. Taken together, the results provide a mechanistic explanation for ITF-mediated protection of gastric epithelial mucosa cells, suggesting that activation of the ERK1/2 signaling pathway may provide a new therapeutic strategy for repairing gastric injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11010-015-2386-2DOI Listing
June 2015

Porous silicon microparticles for delivery of siRNA therapeutics.

J Vis Exp 2015 Jan 15(95):52075. Epub 2015 Jan 15.

Department of Nanomedicine, Houston Methodist Research Institute; Department of Cell and Developmental Biology, Weill Cornell Medical College;

Small interfering RNA (siRNA) can be used to suppress gene expression, thereby providing a new avenue for the treatment of various diseases. However, the successful implementation of siRNA therapy requires the use of delivery platforms that can overcome the major challenges of siRNA delivery, such as enzymatic degradation, low intracellular uptake and lysosomal entrapment. Here, a protocol for the preparation and use of a biocompatible and effective siRNA delivery system is presented. This platform consists of polyethylenimine (PEI) and arginine (Arg)-grafted porous silicon microparticles, which can be loaded with siRNA by performing a simple mixing step. The silicon particles are gradually degraded over time, thereby triggering the formation of Arg-PEI/siRNA nanoparticles. This delivery vehicle provides a means for protecting and internalizing siRNA, without causing cytotoxicity. The major steps of polycation functionalization, particle characterization, and siRNA loading are outlined in detail. In addition, the procedures for determining particle uptake, cytotoxicity, and transfection efficacy are also described.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3791/52075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354534PMC
January 2015

The impact of lubricants on the precision lapping process.

Microsc Microanal 2014 Dec 12;20(6):1708-14. Epub 2014 Nov 12.

4Department of Emergency,Jinling Hospital Medical School of Nanjing University,Nanjing 210000,China.

The impact of lubricants on pole-tip recession and surface morphology of hard disk drive heads in the precision lapping process was investigated with atomic force microscopy, scanning electron microscopy, and auger electron spectroscopy. In particular, the effects of deionized water, hydrocarbon oil, ethanediol, isopropanol, and ethanol lubricants were evaluated. The results reveal that proper selection of lubricant is critical for achieving optimal performance in the lapping process. A mixture of 68% hydrocarbon oil, 30% isopropanol, and 2% octadecenoic acid was found to yield the most favorable results, displaying a writer shield recession, first shield of reader recession, and surface roughness of 0.423, 0.581, and 0.242 nm, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1431927614013397DOI Listing
December 2014

Mechanistic features of nanodiamonds in the lapping of magnetic heads.

ScientificWorldJournal 2014 22;2014:326427. Epub 2014 Jun 22.

Department of Emergency, Jinling Hospital Medical School of Nanjing University, Nanjing 210000, China.

Nanodiamonds, which are the main components of slurry in the precision lapping process of magnetic heads, play an important role in surface quality. This paper studies the mechanistic features of nanodiamond embedment into a Sn plate in the lapping process. This is the first study to develop mathematical models for nanodiamond embedment. Such models can predict the optimum parameters for particle embedment. From the modeling calculations, the embedded pressure satisfies p 0 = (3/2) · (W/πa (2)) and the indentation depth satisfies δ = k1√P/HV. Calculation results reveal that the largest embedded pressure is 731.48 GPa and the critical indentation depth δ is 7 nm. Atomic force microscopy (AFM), scanning electron microscopy (SEM), and Auger electron spectroscopy (AES) were used to carry out surface quality detection and analysis of the disk head. Both the formation of black spots on the surface and the removal rate have an important correlation with the size of nanodiamonds. The results demonstrate that an improved removal rate (21 nm · min(-1)) can be obtained with 100 nm diamonds embedded in the plate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2014/326427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4089205PMC
March 2015