Publications by authors named "Li-Fen Wang"

45 Publications

Sarcopenia as a prognostic predictor of liver cirrhosis: a multicentre study in China.

J Cachexia Sarcopenia Muscle 2021 Sep 14. Epub 2021 Sep 14.

Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China.

Background: Diagnostic criteria for sarcopenia have not been established in Chinese. This study established criteria based on the L3-skeletal muscle index (L3-SMI) and assessed its value for outcomes predicting in cirrhotic Chinese patients.

Methods: Totally 911 subjects who underwent a CT scan at two centres were enrolled in Cohort 1 (394 male and 417 female subjects, aged 20-80 years). The data of those subjects younger than 60 years (365 male and 296 female subjects) were used to determine the reference intervals of the L3-SMI and its influencing factors. Cohort 2 consisted of 480 patients (286 male and 184 female patients) from three centres, and their data were used to investigate the prevalence of sarcopenia and evaluate the value of L3-SMI for predicting the prognosis and complications of cirrhosis.

Results: Age and sex had the greatest effects on the L3-SMI (P < 0.001). The L3-SMI scores were clearly higher in male patients than in female patients (52.94 ± 8.41 vs. 38.91 ± 5.65 cm /m , P < 0.001) and sharply declined in subjects aged ≥ 60 years. Based on the mean -1.28 × SD among adults aged < 60 years, the L3-SMI cut-off value for sarcopenia was 44.77 cm /m in male patients and 32.50 cm /m in female patients. Using these values, 22.5% of the cirrhotic patients (28.7% of male patients and 11.9% of female patients) were diagnosed with sarcopenia. Compared with non-sarcopenia individuals, sarcopenia patients had lower body mass index (21.28 ± 3.01 vs. 24.09 ± 3.39 kg/m , P < 0.001) and serum albumin levels (31.54 ± 5.93 vs. 32.93 ± 5.95 g/L, P = 0.032), longer prothrombin times (16.39 ± 3.05 vs. 15.71 ± 3.20 s, P = 0.049), higher total bilirubin concentrations (41.33 ± 57.38 vs. 32.52 ± 31.48 μmol/L, P = 0.039), worse liver function (Child-Pugh score, 8.05 ± 2.11 vs. 7.32 ± 2.05, P = 0.001), higher prevalence of cirrhosis-related complications (81.82% vs. 62.24%, P < 0.001) and mortality (30.68% vs. 11.22%, P < 0.001). Overall survival was significantly lower in the sarcopenia group [risk ratio (RR) = 2.643, 95% confidence interval (CI) 1.646-4.244, P < 0.001], accompanied with an increased cumulative incidence of ascites (RR = 1.827, 95% CI 1.259-2.651, P = 0.002), spontaneous bacterial peritonitis (RR = 3.331, 95% CI 1.404-7.903, P = 0.006), hepatic encephalopathy (RR = 1.962, 95% CI 1.070-3.600, P = 0.029), and upper gastrointestinal varices (RR = 2.138, 95% CI 1.319-3.466, P = 0.002). Subgroup analysis showed sarcopenia shortened the survival of the patients with Model For End-Stage Liver Disease score > 14 (RR = 4.310, 95% CI 2.091-8.882, P < 0.001) or Child-Pugh C (RR = 3.081, 95% CI 1.516-6.260, P = 0.002).

Conclusions: Sarcopenia is a common comorbidity of cirrhosis and can be used to predict cirrhosis-related complications and the prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcsm.12797DOI Listing
September 2021

Glucose-responsive hydrogel enhances the preventive effect of insulin and liraglutide on diabetic nephropathy of rats.

Acta Biomater 2021 03 11;122:111-132. Epub 2021 Jan 11.

Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China; Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province 325000, China. Electronic address:

Diabetic nephropathy (DN) is one of the most serious complications of diabetes mellitus. The combination of insulin (Ins) with liraglutide (Lir) has a greater potential for preventing DN than monotherapy. However, the renal protective effect of the combined Ins/Lir therapy is largely compromised due to their short half-lives after subcutaneous injection. Herein, a glucose-responsive hydrogel was designed in situ forming the dynamic boronic esters bonds between phenylboronic acid-grafted γ-Polyglutamic acid (PBA-PGA) and konjac glucomannan (KGM). It was hypothesized that the KGM/PBA-PGA hydrogel as the delivery vehicle of Ins/Lir would enhance the combinational effect of the latter on preventing the DN progress. Scan electronic microscopy and rheological studies showed that KGM/PBA-PGA hydrogel displayed good glucose-responsive property. Besides, the glucose-sensitive release profile of either Ins or Lir from KGM/PBA-PGA hydrogel was uniformly displayed at hyperglycemic level. Furthermore, the preventive efficacy of KGM/PBA-PGA hydrogel incorporating insulin and liraglutide (Ins/Lir-H) on DN progress was evaluated on streptozotocin-induced rats with diabetic mellitus (DM). At 6 weeks after subcutaneous injection of Ins/Lir-H, not only the morphology of kidneys was obviously recovered as shown by ultrasonography, but also the renal hemodynamics was significantly improved. Meanwhile, the 24-h urinary protein and albumin/creatinine ratio were well modulated. Inflammation and fibrosis were also largely inhibited. Besides, the glomerular NPHS-2 was obviously elevated after treatment with Ins/Lir-H. The therapeutic mechanism of Ins/Lir-H was highly associated with the alleviation of oxidative stress and activation of autophagy. Conclusively, the better preventive effect of the combined Ins/Lir via KGM/PBA-PGA hydrogel on DN progress was demonstrated as compared with their mixed solution, suggesting KGM/PBA-PGA hydrogel might be a potential vehicle of Ins/Lir to combat the progression of DN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actbio.2021.01.007DOI Listing
March 2021

Bone-Inspired Tube Filling Decellularized Matrix of Toad Cartilage Provided an Osteoinductive Microenvironment for Mesenchymal Stem Cells to Facilitate the Radius Defect Repair of Rabbit.

Biotechnol J 2020 Aug 14;15(8):e2000004. Epub 2020 May 14.

Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province, 325035, China.

Toad bone not only contains the rich cartilage-like matrix but also presents low immunogenicity. It is inferred that decellularized toad bone matrix (dBECM) may provide the more profitable osteoinductive microenvironment for mesenchymal stem cells (MSCs) to promote the repair of bone defects. Herein, a hollow bone-inspired tube is first made from hydroxyapatite (HA) and poly (γ-glutamic acid) (PGA), and then MSCs/dBECM hydrogel is uniformly filled to its central cavity, constructing a biomimetic bone (dBECM + MSCs - PGA + HA). In vitro scratch and transwell experiments show that dBECM hydrogel not only effectively promotes migration and proliferation of MSCs but also induces their osteogenic differentiation. Moreover, the less inflammatory macrophages infiltrate at rat skin after subcutaneously injecting dBECM hydrogel, indicating its low potential for inflammatory attack. After implanting dBECM + MSCs - PGA + HA to critical radius defect of rabbit, X-ray and CT imaging shows that the cortex is effectively regenerated and the medullary cavity recanalization is completed at 20 weeks. Moreover, the expression of Collagen-II and OCN are obviously increased in the defect after implanting dBECM + MSCs - PGA + HA. The therapeutic mechanism of dBECM + MSCs - PGA + HA scaffold are highly associated with the enhanced angiogenesis. Collectively, the biomimetic dBECM + MSCs - PGA + HA scaffold may be a promising strategy to improve radius defect healing efficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/biot.202000004DOI Listing
August 2020

Aloe/poloxamer hydrogel as an injectable β-estradiol delivery scaffold with multi-therapeutic effects to promote endometrial regeneration for intrauterine adhesion treatment.

Eur J Pharm Sci 2020 May 19;148:105316. Epub 2020 Mar 19.

School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China. Electronic address:

Intrauterine adhesion (IUA) is characterized by endometrial stromal replaced with fibrous tissue during the trauma or operation induced injury. Current clinic IUA management mainly involves surgical removal of the connective tissues and physical separation and often results in reoccurrence. It is of clinic interest to directly address the issue via facilitating the endometrial repair and thereby inhibiting the formation of re-adhesion. To this end, we designed a nanocomposite aloe/poloxamer hydrogel for β-estradiol (E2) intrauterine delivery to exert multi-therapeutic effects and promote endometrial regeneration for IUA treatment. Nanoparticulate decellularized uterus (uECMNPs) was prepared to encapsulate E2 ([email protected]), which improved the solubility and prolonged cargo release. Then, [email protected] were further embedded into the thermosensitive aloe-poloxamer hydrogel ([email protected]/AP). Multiple components from [email protected]/AP system could collectively promote proliferation and inhibit apoptosis of endometrial stromal cells. [email protected]/AP significantly increased morphological recovery and decreased uterine fibrosis rate compared with IUA rats in other groups in vivo. Additionally, the levels of Ki67, cytokeratin, and estrogen receptor β were all up-regulated, along with the decreased expression of TGF-β1 and TNF-α in the uterus from rats receiving [email protected]/AP therapy. Taken together, in situ administration of [email protected]/AP hydrogel could effectively promote endometrial regeneration and prevent the re-adhesion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejps.2020.105316DOI Listing
May 2020

Exploring Dual-Substrate Cultivation Strategy of 1,3-Propanediol Production Using Klebsiella pneumoniae.

Appl Biochem Biotechnol 2020 May 20;191(1):346-359. Epub 2019 Dec 20.

Graduate School of Biotechnology and Bioengineering, Yuan Ze University, Chung-Li, Taoyuan, 320, Taiwan.

1,3-Propanediol (1,3-PDO) has numerous industrial applications in the synthesis of the monomer of the widely used fiber polytrimethylene terephthalate. In this work, the production of 1,3-PDO by Klebsiella pneumoniae is increased by dual-substrate cultivation and fed-batch fermentation. Experimental results indicate that the production of 1,3-PDO can be elevated to 16.09 g/L using a dual substrate ratio (of glucose to crude glycerol) of 1/30 and to 20.73 g/L using an optimized dual-substrate ratio of 1/20. Ultimately, the optimal dual-substrate feeding for a 5 L scale fed-batch fermenter that maximizes 1,3-PDO production (29.69 g/L) is determined. This production yield is better than that reported in most related studies. Eventually, the molecular weight and chemical structure of 1,3-PDO were obtained by FAB-MS, H-NMR, and C-NMR. Also, in demonstrating the effectiveness of the fermentation strategy in increasing the production and production yield of 1,3-PDO, experimental results indicate that the fermentation of 1,3-PDO is highly promising for commercialization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12010-019-03208-6DOI Listing
May 2020

Exploiting crosslinked decellularized matrix to achieve uterus regeneration and construction.

Artif Cells Nanomed Biotechnol 2020 Dec;48(1):218-229

School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.

Decellularized extracellular matrix (dECM) has been considered as a promising scaffold in xenotransplantation, yet natural tissue dECM is often mechanically weak and rapidly degraded, compromising the outcomes. How to restore the mechanical strength and optimise the degradation, but maintain the microstructure and maximumly suppress the immune rejection, remains challenging. For this aim, we prepared and characterised various crosslinked decellularized rabbit uterus matrix (dUECM) and evaluated performance after uterus xenotransplantation from rabbit to rat. Naturally derived genipin (GP) and procyanidins (PC) were chosen to crosslink the dUECM, producing significant mechanical enhanced crosslinked-dUECM along with prolonged enzymatic degradation rate. Xenogeneic subcutaneous graft studies revealed that PC- and GP-crosslinked dUECM experienced significant cell infiltration and caused low immune reactions, indicating the desired biocompatibility. transplantation of GP- and PC-crosslinked dUECM to a uterus circular excised rat yielded excellent recellularization ability and promoted uterus regeneration after 90 days. While the reconstruction efficacy of crosslinked dUECM is highly depended on the crosslinking degree, crosslinking condition must be carefully evaluated to balance the role of crosslinked dECM in mechanical and biological support for tissue regeneration promotion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21691401.2019.1699828DOI Listing
December 2020

Cross-linked nanoparticles of silk fibroin with proanthocyanidins as a promising vehicle of indocyanine green for photo-thermal therapy of glioma.

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):4293-4304

Department of Orthopaedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.

Instability of silk fibroin nanoparticles (SFNPs) in physiologic condition hinders its application as drug delivery vehicle. Herein, indocyanine green (ICG) loaded silk fibroin nanoparticles (ICG-SFNPs) was firstly prepared and then crosslinked by proanthocyanidins to obtain the stable ICG-CSFNPs for killing the residual tumour niche under near infra-red irradiation (NIR) after surgery. The particle size and zeta potentials of ICG-CSFNPs was 120.1 nm and -40.4 mV, respectively. Moreover, ICG-CSFNPs exhibited good stability of particle size in the physiological medium. Meanwhile, the stable photothermal properties of ICG-CSFNPs were not compromised even after several cycles of NIR. Few of the ICG-CSFNPs were phagocytized by RAW264.7 macrophage , while they were easily internalized by C6 glioma cells, resulting in their significant toxicity on tumour cells after NIR. The pharmacokinetic study showed that ICG-CSFNPs had a longer blood circulation time than ICG-SFNPs, making them more distribution in glioma after intravenous administration . Meanwhile, the pharmacological study showed the more effective inhibition of tumour growth was exhibited by ICG-CSFNPs in C6 glioma-bearing mice after NIR. Overall, the cross-linked nanoparticles of silk fibroin may be a promising vehicle of ICG for photothermal therapy of glioma after surgical resection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21691401.2019.1699819DOI Listing
December 2019

Ectoine production with indigenous sp. MAR2 isolated from the marine environment.

Prep Biochem Biotechnol 2020 13;50(1):74-81. Epub 2019 Sep 13.

Graduate School of Biotechnology and Bioengineering, Yuan Ze University, Taoyuan, Taiwan (R.O.C.).

Ectoine has fostered the development of products for skin care and cosmetics. In this study, we employed the marine bacterial strain sp. MAR2 to increase ectoine production by optimizing medium constituents using Response Surface Methodology (RSM) and a fed-batch strategy. The results from the steepest ascent and central composite design indicated that 54 g/L of yeast extract, 14.0 g/L of ammonium acetate, 74.4 g/L of sodium glutamate, and 6.2 g/L of sodium citrate constituted the optimal medium with maximum ectoine production (3.5 g/L). In addition, we performed fed-batch culture in the bioreactor, combining pH and dissolved oxygen to produce ectoine by sp. MAR2. The ectoine production, content, and productivity of 5.6 g/L, 10%, and 3.9 g/L/day were further reached by a fed-batch culture. Thus, the ectoine production by sp. MAR2 using RSM and fed-batch strategy shows its potential for industrial production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10826068.2019.1663534DOI Listing
February 2020

Enhancing production of lutein by a mixotrophic cultivation system using microalga Scenedesmus obliquus CWL-1.

Bioresour Technol 2019 Nov 26;291:121891. Epub 2019 Jul 26.

Graduate School of Biotechnology and Bioengineering, Yuan Ze University, No. 135, Yuan-Tung Road, Chung-Li Dist, Taoyuan City 32003, Taiwan, ROC. Electronic address:

This work studies a series of strategies in the production of lutein by Scenedesmus obliquus CWL-1 under mixotrophic cultivation. Our experimental results revealed that the optimal conditions associated with light-related strategies were 12 h light period followed by a 12 h dark period and blue to red light under mixotrophic cultivation. Under such conditions, the biomass, lutein content and lutein productivity were maximized to 9.88 (g/L), 1.78 (mg/g) and 1.43 (mg/L/day), respectively. Moreover, the assimilation of 4.5 g/L of calcium nitrate into S. obliquus CWL-1 increased the maximal biomass (12.73 g/L) and the highest maximal lutein productivity (3.06 mg/L/day), while the assimilation of 1.5 g/L of calcium nitrate yielded the highest maximal lutein content of 2.45 mg/g. The highest maximal lutein productivity of 4.96 (mg/L/day) was obtained when fed-batch fermentation was conducted, and this value was approximately 11-folds that obtained using the batch system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biortech.2019.121891DOI Listing
November 2019

Bilirubin Improves the Quality and Function of Hypothermic Preserved Islets by Its Antioxidative and Anti-inflammatory Effect.

Transplantation 2019 12;103(12):2486-2496

School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province, China.

Background: Islet transplantation is a promising option for the treatment of type 1 diabetes. However, the current lack of practical techniques for the isolated islets preservation still hampers the advancement of life-saving islet transplantation. Islet suffers from internal or external stimuli-induced oxidative stress and subsequent inflammation during preservation, which leads to disappointing outcomes regarding islet yield, survival, and function. Reactive oxygen species (ROS) overproduction is the primary cause of oxidative stress that induces islet loss and dysfunction. Thus, in this article, we hypothesized that an endogenous antioxidant, bilirubin, that could efficiently scavenge ROS and inhibit inflammatory reactions could be beneficial for islet preservation.

Methods: Herein, we studied the effect of bilirubin on the hypothermic preserved (4°C) islets and evaluate the islets viability, insulin secretory function, oxidative stress levels, and in vivo transplantation performance.

Results: Bilirubin could prevent cellular damages during short-term preservation and maintain the cocultured islets viability and function. The protective role of bilirubin is associated with its antioxidative ability, which dramatically increased the activities of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) and decreased the levels of ROS and malondialdehyde. Diabetic mice transplanted with bilirubin preserved islets were normoglycemic for 28 days, even overmatched the diabetic mouse transplanted with fresh islets. Mice receiving bilirubin cocultured islets required the least time to achieve normoglycemia among all groups and exhibited minimum inflammatory responses during the early transplantation stage.

Conclusions: By utilizing bilirubin, we achieved highly viable and functional islets after hypothermic preservation to reverse diabetes in mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000002882DOI Listing
December 2019

Thiolated γ-polyglutamic acid as a bioadhesive hydrogel-forming material: evaluation of gelation, bioadhesive properties and sustained release of KGF in the repair of injured corneas.

Biomater Sci 2019 May;7(6):2582-2599

Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China.

Keratinocyte growth factor (KGF) has a good therapeutic effect on injured corneas. However, due to the washout of tears and blinking, locally administrated KGF usually has a short residence time on the surface of an injured cornea, resulting in its poor bioavailability. Herein, a bioadhesive hydrogel is described produced using cysteine-modified γ-polyglutamic acid (PGA-Cys) as the hydrogel-forming material to locally deliver KGF. A series of PGA-Cys polymers with different graft ratios of cysteine were firstly synthesized and carefully characterized. Thereafter, the PGA-Cys hydrogel was screened by changing the graft ratio of cysteine and polymer concentration, and the apparent viscosities and bioadhesive force were also carefully investigated. It was found that PGA-Cys polymers with different graft ratios of cysteine exhibited tunable apparent viscosity and bioadhesive properties at the same polymer concentration. When PGA-Cys with a graft ratio of 1.5 mmol g-1 of cysteine (PGA-Cys-1.5) was used as hydrogel-forming material, the hydrogel exhibited a good gelation property with an apparent viscosity of 5.2 Pa s and strong bioadhesive force of 167 ± 0.5 mN. In vitro release study showed that KGF was slowly released from PGA-Cys-1.5 hydrogel over a longer time in comparison to PGA solution alone. Moreover, PGA-Cys-1.5 hydrogel enabled most of the encapsulated KGF to be retained on the cornea and conjunctiva after local administration. Meanwhile, the morphology of the corneal epithelium in the alkali-injured cornea of mice was well repaired after 7 days of treatment with KGF-PGA-Cys-1.5 hydrogel. The therapeutic mechanism was strongly associated with inhibiting corneal inflammation and neovascularization, promoting proliferation of the corneal epithelium and inhibiting apoptosis. Overall, the use of the bioadhesive PGA-Cys hydrogel with a suitable KGF release profile may be a more promising approach than using PGA solution alone and KGF to repair injured corneas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9bm00341jDOI Listing
May 2019

Exploring useful fermentation strategies for the production of hydroxyectoine with a halophilic strain, Halomonas salina BCRC 17875.

J Biosci Bioeng 2019 Sep 29;128(3):332-336. Epub 2019 Mar 29.

Graduate School of Biotechnology and Bioengineering, Yuan Ze University, No. 135 Yuan-Tung Rd., Chung-Li Dist., Taoyuan City 32003, Taiwan, ROC. Electronic address:

Hydroxyectoine, an ectoine derivative, is the most common compatible solute in halophilic microorganisms for resisting harsh environments. Compatible solutes can be utilized in fields such as cosmetics, medicine, and biochemistry. Moderately halophilic microorganisms produce much less hydroxyectoine as compared with ectoine. In this study, we first evaluate the effect of medium formulation (i.e., yeast extract (YE) medium and high yeast extract (HYE) medium) on hydroxyectoine production. In addition, an investigation of hydroxyectoine production by Halomonas salina under optimal conditions for vital factors (i.e., iron and α-ketoglutarate) and hydroxylase activity was also carried out. As a result, hydroxyectoine production was obviously elevated (0.9 g/L to 1.8 g/L) when the HYE medium was utilized. Furthermore, hydroxyectoine production further increased to 2.4 g/L when both the α-ketoglutarate and iron factors were added to the HYE medium in the early stationary phase. In addition, we found that ectoine hydroxylase activity increased more when a combination of iron and α-ketoglutarate was used than when either was used alone. The results showed that the alteration of iron and α-ketoglutarate clearly stimulated the expression of ectoine hydroxylase, which in turn affected hydroxyectoine synthesis. This study also showed that hydroxyectoine production was further raised from 2.4 g/L to 2.9 g/L when 50 mM of α-ketoglutarate and 1 mM of iron were added to the HYE medium. Ultimately, the experimental results showed using the optimal conditions further elevated the hydroxyectoine production yield to 2.90 g/L, which was over 3-fold higher than the best results obtained from the original medium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbiosc.2019.02.015DOI Listing
September 2019

The pattern-recognition molecule mindin binds integrin Mac-1 to promote macrophage phagocytosis via Syk activation and NF-κB p65 translocation.

J Cell Mol Med 2019 05 14;23(5):3402-3416. Epub 2019 Mar 14.

Department of Gastroenterology, Zhongshan Hospital affiliated to Xiamen University, Xiamen, China.

Mindin has a broad spectrum of roles in the innate immune system, including in macrophage migration, antigen phagocytosis and cytokine production. Mindin functions as a pattern-recognition molecule for microbial pathogens. However, the underlying mechanisms of mindin-mediated phagocytosis and its exact membrane receptors are not well established. Herein, we generated mindin-deficient mice using the CRISPR-Cas9 system and show that peritoneal macrophages from mindin-deficient mice were severely defective in their ability to phagocytize E  coli. Phagocytosis was enhanced when E  coli or fluorescent particles were pre-incubated with mindin, indicating that mindin binds directly to bacteria or non-pathogen particles and promotes phagocytosis. We defined that I-labelled mindin binds with integrin Mac-1 (CD11b/CD18), the F-spondin (FS)-fragment of mindin binds with the α -I domain of Mac-1 and that mindin serves as a novel ligand of Mac-1. Blockade of the α -I domain of Mac-1 using either a neutralizing antibody or si-Mac-1 efficiently blocked mindin-induced phagocytosis. Furthermore, mindin activated the Syk and MAPK signalling pathways and promoted NF-κB entry into the nucleus. Our data indicate that mindin binds with the integrin Mac-1 to promote macrophage phagocytosis through Syk activation and NF-κB p65 translocation, suggesting that the mindin/Mac-1 axis plays a critical role during innate immune responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.14236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484411PMC
May 2019

MMP-1 is overexpressed in triple-negative breast cancer tissues and the knockdown of MMP-1 expression inhibits tumor cell malignant behaviors .

Oncol Lett 2019 Feb 30;17(2):1732-1740. Epub 2018 Nov 30.

Department of Pathology, The Second Hospital, Dalian Medical University, Dalian, Liaoning 116027, P.R. China.

Matrix metalloproteinase 1 (MMP-1) is a member of the zinc-dependent endopeptidase family, which cleaves the extracellular matrix. The present study investigated the functional role of MMP-1 in breast cancer and in order to determine the underlying molecular mechanisms. The levels of MMP-1 were analyzed in 99 breast cancer specimens using immunohistochemistry and western blotting. A stable short hairpin RNA (shRNA) knockdown of MMP-1 expression was performed in MCF-7 and MDA-MB-231 breast cancer cells, and the effects were examined using MTT and colony formation assays, as well as migration and invasion assays, while western blotting was used to detect the activation of intracellular signaling. The MMP-1 protein was more highly expressed in triple-negative breast cancer tissues than in estrogen receptor(+) and human epidermal growth factor 2 receptor(3+) breast cancer tissues (P<0.05). Furthermore, the MMP-1 levels were significantly higher in the tumor and tumor stromal cells of lymph node metastatic breast cancer tissues than in those of non-metastatic tissues. The knockdown of MMP-1 expression in MCF-7 and MDA-MB-231 cells using MMP-1 shRNA significantly inhibited cell proliferation, migration and invasion, and the expression of the Myc proto-oncogene protein, phosphorylated and total RAC-α serine/threonine-protein kinase 1, and B-cell lymphoma 2, but increased the protein levels of apoptosis regulator BAX and caspase 3. In conclusion, the data suggest that MMP-1 serves an important role in breast cancer development and metastasis. Future studies should assess MMP-1 as a prognostic marker for patients with breast cancer and its inhibition as a novel strategy for controlling breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2018.9779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341686PMC
February 2019

Liraglutide ameliorates beta-cell function, alleviates oxidative stress and inhibits low grade inflammation in young patients with new-onset type 2 diabetes.

Diabetol Metab Syndr 2018 17;10:91. Epub 2018 Dec 17.

1Department of Endocrinology and Metabolism, Zhongshan Hospital Xiamen University, 201-209 Hubin South Road, Xiamen, 361004 China.

Background: The prevalence of type 2 diabetes in youth is escalating rapidly. We aimed to evaluate the effects of liraglutide on beta-cell function, metabolic productions of oxidative stress, low grade inflammation compared with metformin in young patients with recent onset type 2 diabetes mellitus.

Methods: Sixty patients were randomly assigned to receive 8-week liraglutide or metformin treatment. Beta-cell function was assessed by modified beta cell function index (MBCI), early phase of insulin secretion index (ΔI30/ΔG30), proinsuin to insulin ratio (P/I) and the insulin area under the curve (AUCins). The expression of 8-OH-dG and 8-iso-PGF and hs-C-reactive protein (hs-CRP) were measured as indications of oxidative stress and low grade inflammation.

Results: After 8 weeks liraglutide treatment, MBCI, ΔI30/ΔG30, AUCins significantly increased, 8-OH-dG, 8-iso-PGF, P/I and hs-CRP remarkably reduced. The differences before and after 8-week liraglutide treatment in ΔMBCI (11.1 [2.81, 43.08] vs 0.00 [- 8.16, 10.47], P = 0.017), ΔLNΔI30/ΔG30 (0.44 [0.04, 0.85] vs - 0.09 [- 0.33, 0.36], P = 0.049), ΔAUCins (117 [- 8, 376] vs - 21 [- 314, 109] mIU/L, P = 0.013), ΔP/I (- 0.05 [- 0.09, - 0.03] vs - 0.02 [- 0.04, 0.01], P = 0.026)were remarkably enhanced compared to those of the metformin therapy. The expression of 8-OH-dG, 8-iso-PGF and hs-CRP also decreased after 8-week metformin treatment.

Conclusions: These data demonstrated that liraglutide administration was more effective on ameliorating beta-cell function than metformin treatment in young patients with new-onset type 2 diabetes mellitus. Both liraglutide and metformin could alleviate the level of oxidative stress and attenuate low grade inflammatory, we speculate this effect may not the main mechanism of beta-cell function improvement by liraglutide in diabetic patients. Chinese Clinical Trials registry, chiCTR1800018008, Registered 27 August 2018-retrospectively registered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13098-018-0392-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6296090PMC
December 2018

Construction and co-cultivation of two mutant strains harboring key precursor genes to produce prodigiosin.

J Biosci Bioeng 2018 Dec 29;126(6):783-789. Epub 2018 Jun 29.

Graduate School of Biotechnology and Bioengineering, Yuan Ze University, No. 135, Yuan-Tung Road, Chung-Li Dist., Taoyuan City 32003, Taiwan, ROC. Electronic address:

The biosynthesis of prodigiosin (PG) from Serratia marcescens involves the coupling of a bipyrrole, 4-methoxy-2,2'-bipyrrole-5-carboxaldehyde (MBC), with a monopyrrole, 2-methyl-3-n-amyl-pyrrole (MAP), and formation of a linear tripyrrole (PG). We constructed mutant strains in which either the MBC biosynthesis by S. marcescens BMJ816 or the MAP biosynthesis by S. marcescens AMJ817. S. marcescens BMJ816 and AMJ817 confirmed that they lose the ability to synthesize PG when they are cultivated alone. An experiment was also conducted in which cultures of the two mutant strains were grown to the early exponential phase in a semi-defined medium, and one suspension culture was inoculated with the other. This approach yielded 103 mg/L PG. The findings suggest that the addition of precursors may enhance PG production by microorganisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbiosc.2018.06.010DOI Listing
December 2018

Skin-permeable liposome improved stability and permeability of bFGF against skin of mice with deep second degree scald to promote hair follicle neogenesis through inhibition of scar formation.

Colloids Surf B Biointerfaces 2018 Dec 5;172:573-585. Epub 2018 Sep 5.

Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, China. Electronic address:

Excessive deposition of extracellular matrix (ECM) usually resulted in scar formation during wound healing, which caused skin dysfunction, such as hair loss. Basic fibroblast growth factor (bFGF) was very helpful for promoting hair follicle neogenesis and regulating the remodeling of ECM during wound healing. Because of its poor stability in wound fluids and low permeability against the dense wound scar, the repairing quality of bFGF on wound was hindered largely in clinical practice. To overcome these drawbacks, herein, a novel liposome with silk fibroin hydrogel core (bFGF-SF-LIP) was firstly prepared to stabilize bFGF, followed by insertion of laurocapam, a permeation enhancer, into the liposomal membrane to construct a skin-permeable liposome (SP-bFGF-SF-LIP). The encapsulated efficiency of bFGF was reaching to nearly 90% when ratio of drug/lipids above 1:300, and it activity was not compromised by laurocapam. SP-bFGF-SF-LIP exhibited a hydrodynamic diameter of 103.3 nm and Zeta potential of -2.31 mV. The stability of the encapsulated bFGF in wound fluid was obviously enhanced. After 24 h of incubation with wound fluid containing MMP-9, the remaining bFGF was as high as 65.4 ± 0.5% for SP-bFGF-SF-LIP, while only 2.1 ± 0.2% of free bFGF was remained. The skin-permeability of bFGF was significantly enhanced by SP-bFGF-SF-LIP and most of the encapsulated bFGF penetrated into the dermis. After treatment with SP-bFGF-SF-LIP, the morphology of hair follicle at wound zone was obviously improved and the hair regrew on the deep second scald mice model. The therapeutic mechanism was highly associated with inhibiting scar formation and promoting vascular growth in dermis. Conclusively, SP-bFGF-SF-LIP may a potential option to improve wound healing with high-quality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.colsurfb.2018.09.006DOI Listing
December 2018

Liraglutide suppresses non-esterified free fatty acids and soluble vascular cell adhesion molecule-1 compared with metformin in patients with recent-onset type 2 diabetes.

Cardiovasc Diabetol 2018 04 10;17(1):53. Epub 2018 Apr 10.

Department of Endocrinology and Metabolism, Zhongshan Hospital Xiamen University, 201-209 Hubin South Road, Xiamen, 361004, People's Republic of China.

Background: It has been suggested that liraglutide could have an impact on glucose and lipid metabolism disorder and adhesion molecule activation, which may play important roles in the vascular damage of diabetes. In this study, we examined the effects of liraglutide versus metformin on non-esterified free fatty acids, beta-cell insulin secretion, and adhesion molecule levels in patients with recent-onset type 2 diabetes mellitus.

Methods: In this study, 60 patients newly diagnosed with type 2 diabetes mellitus (mean age 33.97 ± 5.67 years) were randomly assigned to receive once-daily subcutaneous liraglutide or oral metformin. Before the study and after the 8-week treatment period, a 75 g oral glucose tolerance test was performed. Plasma glucose, lipids and lipoprotein, plasma insulin, glycaemic and insulin responses, non-esterified free fatty acids (NEFA), and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were evaluated.

Results: After 8 weeks, 120 min of NEFA (155 ± 125 vs 99 ± 73 µmol/L, P = 0.026) and the levels of sVCAM-1 (465 ± 136 vs 382 ± 131 ng/ml, P = 0.013) significantly decreased, while the early phase insulin secretion index (24.94 [7.78, 38.89] vs. 31.13 [17.67, 59.09], P = 0.031), fasting plasma insulin (104 [51, 123] vs 113 [54, 171] mIU/L, P = 0.015), 60 min plasma insulin (326 [165, 441] vs 471 [334, 717] mIU/L, P = 0.005), 120 min plasma insulin (401 [193, 560] vs 500 [367, 960] mIU/L, P = 0.047), and insulin area under the curve (AUCins) (648 [321, 742] vs 738 [451, 1118] mIU/L, P = 0.005) remarkably increased for patients in the liraglutide treatment group. The levels of sVCAM-1 dramatically decreased after 8 weeks of liraglutide treatment (503 ± 182 vs 382 ± 131 ng/ml, P = 0.046) compared to that of the metformin treatment group. At the same time, the differences before and after liraglutide treatment in 120 min of NEFA (- 32 [- 96, - 5] vs 5 [- 35, 38] µmol/L, P = 0.033) and AUCins (738 [451, 1118] vs 594 [357, 1216] mIU/L, P = 0.014) were remarkably enhanced compared to that of the metformin therapy. Nevertheless, there were no significant differences in fasting NEFA after liraglutide or metformin treatment. The reduction of 120 min NEFA (ΔNEFA) was positively correlated with the decrease of sVCAM-1 (ΔsVCAM-1) after 8 weeks of liraglutide treatment (r = 0.523, P = 0.003).

Conclusions: Our results demonstrate that liraglutide administration is more effective than metformin in reducing 120 min NEFA and suppressing sVCAM-1 levels for recent-onset type 2 diabetes mellitus. We suggest that this outcome may be because liraglutide is associated with potentiating insulin secretion capacity, inhibiting vascular inflammatory cytokines, and antagonizing atherosclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12933-018-0701-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891985PMC
April 2018

CoQ10-loaded liposomes combined with UTMD prevented early nephropathy of diabetic rats.

Oncotarget 2018 Feb 19;9(14):11767-11782. Epub 2018 Jan 19.

Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province, China.

Nephropathy is one of the most severe complications of diabetic patients. The therapeutic strategies for diabetic patients should not only focus on the control of blood glucose but also pay attention to the occurrence of diabetic nephropathy (DN). Coenzyme Q10 (CoQ10) has great therapeutic potential for DN. However, the clinical application of CoQ10 has been limited because of its low water-solubility and non-specific distribution. Liposomes were supposed to be an effective way for delivering CoQ10 to kidney. CoQ10 was effectively encapsulated into the liposome (CoQ10-LIP) with a high entrapment efficiency of 86.15 %. The CoQ10-LIP exhibited a small hydrodynamic diameter (180 ± 2.1 nm) and negative zeta potential (-18.20 mV). Moreover, CoQ10-LIP was combined with ultrasound-mediated microbubble destruction (UTMD) to enhance specific distribution of CoQ10 in kidney. In early stage of diabetic mellitus (DM), rats were administrated with CoQ10-LIP followed by UTMD (CoQ10-LIP+UTMD) to prevent occurrence of DN. Results revealed that CoQ10-LIP+UTMD effectively prevented the renal morphology and function of diabetics rats from damage. The protective mechanism of CoQ10-LIP was highly associated with protecting podocyte, promoting vascular repair and inhibiting cell apoptosis. Conclusively, CoQ10-LIP in combination with UTMD might be a potential strategy to prevent occurrence of DN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.24363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837748PMC
February 2018

Production and characterization of ectoine using a moderately halophilic strain Halomonas salina BCRC17875.

J Biosci Bioeng 2018 May 11;125(5):578-584. Epub 2018 Jan 11.

Graduate School of Biotechnology and Bioengineering, Yuan Ze University, No. 135 Yuan-Tung Road, Chung-Li Dist., Taoyuan 32003, Taiwan, ROC. Electronic address:

This study attempted to utilize Halomonas salina BCRC17875 to produce ectoine by optimizing the agitation speed and medium composition. In addition, the chemical structure of ectoine produced by H. salina BCRC17875 was determined. The results indicate that ectoine production reached 3.65 g/L at 38 h of cultivation when the agitation rate and NaCl concentration were fixed at 200 rpm and 2.0 M, respectively. It reached 9.20 g/L at 44 h of cultivation when the major medium components were yeast extract (56 g/L), glutamate (74.40 g/L), and ammonium sulfate (14 g/L). After the nitrogen concentration had been evaluated, evaluation of the nitrogen concentration revealed that the ectoine production reached 11.80 g/L at 44 h of cultivation when 56 g/L of yeast extract and 28 g/L of ammonium sulfate were used. Ectoine production reached 13.96 g/L at 44 h of cultivation when the carbon/nitrogen ratio was fixed at 3/1 using 84 g/L of yeast extract and 28 g/L of ammonium sulfate. Furthermore, the identification of ectoine were identified and characterized by fast atom bombardment mass spectrometry (FAB-MS) and H NMR. The results demonstrated a fermentation strategy was successful in increasing ectoine production, and that the fermentation medium of ectoine had commercialization potential.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbiosc.2017.12.011DOI Listing
May 2018

[Association of heart valve calcification with cardiovascular outcomes in patients on maintenance hemodialysis].

Nan Fang Yi Ke Da Xue Xue Bao 2016 Jun;36(7):941-6

Southern Medical University, Guangzhou 510515, China.E-mail:

Objective: To investigate the impact of heart valve calcification (HVC) on cardiovascular outcomes in patients on maintenance hemodialysis (MHD).

Methods: We enrolled 302 Chinese patients on MHD between 2009 and 2011 including 99 with HVC identified by echocardiography screening. All the patients were followed up for 2 years and survival analysis was performed with all-cause mortality, cardiovascular mortality and new onset cardiovascular events as the endpoints. Cox regression analysis was used for analyzing the impact of heart valve calcification on the cardiovascular outcomes of the patients.

Results: The mean age of the total patients was 58.2∓15.0 years when receiving the initial MHD, and 53.6% were male patients. The overall mortality, cardiovascular mortality and new on-set cardiovascular events in HVC and non-HVC groups were 30.3% vs 16.3%, 22.2% vs 6.9%, and 48.5% vs 25.6%, respectively (P<0.05). Kaplan-Meier survival analysis showed a significant difference in all-cause mortality (P=0.006), cardiovascular mortality (P<0.001) and new-onset cardiovascular events (P<0.001) between HVC and non-HVC groups. After adjustment, Cox regression analysis identified HVC as a risk factor for increased all-cause mortality (HR=1.88; 95%CI: 1.11-3.19), cardiovascular mortality (HR=3.47, 95%CI: 1.76-6.84) and cardiovascular events (HR=1.64, 95% CI: 1.09-2.47).

Conclusions: HVC is an independent risk factor for increased cardiovascular mortality and new cardiovascular events in patients on MHD.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2016

Dragon (RGMb) induces oxaliplatin resistance in colon cancer cells.

Oncotarget 2016 07;7(30):48027-48037

Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer mortality. Chemotherapy resistance remains a major challenge for treating advanced CRC. Therefore, the identification of targets that induce drug resistance is a priority for the development of novel agents to overcome resistance. Dragon (also known as RGMb) is a member of the repulsive guidance molecule (RGM) family. We previously showed that Dragon expression increases with CRC progression in human patients. In the present study, we found that Dragon inhibited apoptosis and increased viability of CMT93 and HCT116 cells in the presence of oxaliplatin. Dragon induced resistance of xenograft tumor to oxaliplatinin treatment in mice. Mechanistically, Dragon inhibited oxaliplatin-induced JNK and p38 MAPK activation, and caspase-3 and PARP cleavages. Our results indicate that Dragon may be a novel target that induces drug resistance in CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.10338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216997PMC
July 2016

Overexpression of sucrose transporter gene PbSUT2 from Pyrus bretschneideri, enhances sucrose content in Solanum lycopersicum fruit.

Plant Physiol Biochem 2016 Aug 13;105:150-161. Epub 2016 Apr 13.

Center of Pear Engineering & Technology Research, College of Horticulture, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address:

Sucrose transporters (SUTs) belong to the major facilitator superfamily. The function of SUTs has been intensively investigated in some higher plants, whereas that in pear fruit is unknown. In this study, the cloning and functional characterization of a sucrose transporter, PbSUT2, in pear (Pyrus bretschneideri Rehd. cv. 'Yali') fruits are reported. PbSUT2 encoded a protein of 498 amino acid residues, and was localized in the plasma membrane of transformed onion epidermal cells and Arabidopsis protoplasts. Phylogenetic analysis revealed that PbSUT2 belonged to the SUT4 clade. The phenotype of overexpression of PbSUT2 tomato plants included early flowering, higher fruit quantity and lower plant height. Overexpression of PbSUT2 in transgenic tomato plants led to increases in the net photosynthetic rate in leaves and sucrose content in mature fruit compared with wild-type tomato plants, and a decrease in the contents of glucose, fructose and total soluble sugars in mature fruits. These results suggested that PbSUT2 affected sucrose content in sinks and the flowering phase during tomato plant growth and development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.plaphy.2016.04.019DOI Listing
August 2016

Characterization and Curing Kinetics of Epoxy/Silica Nano-Hybrids.

Materials (Basel) 2015 Oct 16;8(10):7032-7040. Epub 2015 Oct 16.

Department of Chemical and Materials Engineering, National University of Kaohsiung, No. 700, Kaohsiung University Rd., Nan-Tzu Dist., Kaohsiung 811, Taiwan.

The sol-gel technique was used to prepare epoxy/silica nano-hybrids. The thermal characteristics, curing kinetics and structure of epoxy/silica nano-hybrids were studied using differential scanning calorimetry (DSC), Si nuclear magnetic resonance (NMR) and transmission electron microscopy (TEM). To improve the compatibility between the organic and inorganic phases, a coupling agent was used to modify the diglycidyl ether of bisphenol A (DGEBA) epoxy. The sol-gel technique enables the silica to be successfully incorporated into the network of the hybrids, increasing the thermal stability and improving the mechanical properties of the prepared epoxy/silica nano-hybrids. An autocatalytic mechanism of the epoxy/SiO₂ nanocomposites was observed. The low reaction rate of epoxy in the nanocomposites is caused by the steric hindrance in the network of hybrids that arises from the consuming of epoxide group in the network of hybrids by the silica. In the nanocomposites, the nano-scale silica particles had an average size of approximately 35 nm, and the particles were well dispersed in the epoxy matrix, according to the TEM images.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ma8105357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455391PMC
October 2015

Two new steroidal glycosides from Cynanchum otophyllum Schneid.

J Asian Nat Prod Res 2015 7;17(3):285-8. Epub 2014 Oct 7.

a College of Pharmacy, Liaoning University of Traditional Chinese Medicine , Dalian 116600 , China.

Two new C21 steroidal glycosides were isolated from Cynanchum otophyllum Schneid. Their structures were elucidated as qinyangshengenin-3-O-β-d-digitoxopyranoside (1) and rostratamine-3-O-β-d-cymaropyranosyl-(1 → 4)-β-d-digitoxopyranoside (2) on the basis of chemical and spectroscopic methods, including 1D and 2D NMR experiments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10286020.2014.956308DOI Listing
June 2015

An eye-tracking assistive device improves the quality of life for ALS patients and reduces the caregivers' burden.

J Mot Behav 2014 14;46(4):233-8. Epub 2014 Apr 14.

a School of Medicine , National Yang Ming University , Taipei , Taiwan.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. In some cases, patients with ALS retain a normal level of consciousness but disease progression eventually results in generalized paralysis, which first impedes and then prevents oral communication. This communication obstacle can generate a great deal of stress for the patient, family, and caregiver. Here the authors ask whether the use of an eye-tracking assistive device can improve quality of life for ALS patients and relieves burden of their primary caregivers. Subjects were divided into two groups depending on whether they used (n = 10) or did not use (n = 10) an eye-tracking assistive device. The authors assessed patients' quality of life and severity of depression using the ALS Specific Quality of Life Instrument-Revised and the Taiwanese Depression Questionnaire, respectively. The Caregiver Burden Scale was used to assess the burden on caregivers. Our study shows that the eye-tracking assistive device significantly improved patients' quality of life, as compared with patients in the nonuser group (p <.01). The assistive device also reduced the burden on caregivers (p <.05). This is likely a result of the improvement of patient's autonomy and more effective communication between patient and caregiver.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00222895.2014.891970DOI Listing
January 2015

[Primary mechanism of the role of dual oxidase-1 causing airway allergic diseases in human bronchial epithelium].

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2013 Oct;48(10):823-9

Department of Otorhinolarynology Head and Neck Surgery, Zhongda Hospital, Southeast University, Nanjing 210009, China.

Objective: To investigate the role of dual oxidase-1 (DUOX-1) inducing airway hyperresponsiveness in human bronchial epithelium.

Methods: The human bronchial epithelial cells were divided into several groups: control group, tumor necrosis factor-α (TNF-α) group, methyl-β-cyclodextrin (M-β-CD)+TNF-α group, desipramine (DES)+ TNF-α group, diphenylene iodonium (DPI) + TNF-α group and apocynin (APO)+TNF-α group. Fractionation was performed by sucrose gradient centrifugation and the protein DUOX-1 was measured by western blotting. The lipid raft clusters and its colocalization with DUOX-1 were confocal analysed. The intracellular reactive oxygen species (ROS) accumulation was measured by fluorescence of reactive oxygen probe of intracellular measurement. Sigmastat 3.02 software was used to analyze the data.

Results: (1) Detection of ROS, control group: 1.00 ± 0.00; TNF-α group: 1.95 ± 0.16; M-β-CD+TNF-α group: 0.91 ± 0.16; DES+TNF-α group: 1.49 ± 0.20; DPI+TNF-α group: 1.03 ± 0.16; APO+TNF-α group: 1.47 ± 0.26. The difference was statistically significant (F = 3.83, P < 0.05). (2) Extracts in rafts to lipid rafts region represents the ratio of total protein, protein content DUOX-1 each group, control group: 0.21 ± 0.02; TNF-α group: 0.49 ± 0.04; M-β-CD+TNF-α group: 0.08 ± 0.02; DES+TNF-α group: 0.09 ± 0.03; the difference was statistically significant (F = 3.96, P < 0.05). (3) DUOX-1 protein fluorescence values, control group: 1.72 ± 0.21; TNF-α group: 8.11 ± 1.23; M-β-CD+TNF-α group: 1.51 ± 0.32; DES+TNF-α group: 1.43 ± 0.11; the difference was statistically significant (F = 4.87, P < 0.05). (4) DUOX-1 gene detection, control group: 1.00 ± 0.00 ScrRNA+TNF-α group: 1.75 ± 0.04; DUOX-1siRNA+TNF-αgroup: 1.15 ± 0.02; the difference was statistically significant (F = 4.19, P < 0.05).

Conclusion: TNF-α can induce DUOX-1 expression increasing in lipid raft, then the DUOX-1 can be activated to increase reactive oxygen species level; acidic sphingomyelinase inhibitor desipramine can inhibit this process, the results disclose that the process will depend on the ceramide of lipid raft.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2013

[The difference of IL-28B polymorphisms between hepatitis C patients with and without cryoglobulinemia].

Zhonghua Gan Zang Bing Za Zhi 2013 Jun;21(6):429-33

Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China.

Objective: To determine whether patients infected with chronic hepatitis C (CHC) show a differential distribution profile of IL-28B polymorphisms according to the presence of concomitant cryoglobulinemia.

Methods: Sixty-two consecutive CHC patients were enrolled in the study between December 2008 and December 2010. All patients received combination therapy of pegylated interferon alpha-2a (weekly, 180 g, subcutaneous injection) plus ribavirin (daily, 10to15 mg/kg body weight, oral) for 48 weeks, with individualized dosage adjustments according to the patient's clinical situation. Cryoglobulins were detected visibly by separation of cryoprecipitates in patient serum samples. Three IL-28B SNPs (rs8099917, rs12979860, and rs12980275) were detected by sequencing. Response to treatment was assessed by measuring serum levels of HCV RNA by quantitative PCR at baseline (prior to treatment initiation), during treatment (4 and 12 weeks after treatment initiation), end of therapy (48 weeks after treatment initiation), and post-treatment (24 weeks after end of therapy). The significance of between-group differences were assessed by the Chi-square and Fisher's exact tests.

Results: Cryoglobulinemia was detected in 43.5% (27/62) of the CHC patients and showed a female bias (59.3% vs. males: 34.3%, P = 0.05). Compared to CHC patients without cryoglobulinemia, the CHC patients with cryoglobulinemia showed significantly higher levels of HCV RNA at baseline (5.64+/-1.20 vs. 6.37+/-0.67, P less than 0.05) but lower frequencies of the IL28B rs8099917 TT genotype (94.3% vs. 63.0%, P = 0.002), rs8099917 T allele (97.1% vs. 81.5%, P = 0.003), and rs12979860 C allele (94.3% vs. 83.3%, P = 0.048). CHC patients with cryoglobulinemia and having the rs8099917 TT, rs12979860 CC, or rs12980275 AA genotype achieved a higher rate of sustained virological response.

Conclusion: Cryoglobulinemia in CHC patients is associated with a differential distribution of IL-28B polymorphisms, and certain polymorphisms may be related to anti-viral treatment response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3760/cma.j.issn.1007-3418.2013.06.011DOI Listing
June 2013

Cryoglobulinemia is an independent factor negatively associated with sustained virological response in chronic hepatitis C patients.

Chin Med J (Engl) 2012 Nov;125(22):4014-7

Department of Infectious Diseases, Peking University First Hospital, Beijing, China.

Background: Mixed cryoglobulinemia (MC) is one of the most common and severe symptoms in chronic hepatitis C patients. The aim of this study was to investigate whether mixed cryoglobulinemia is a factor associated with sustained virological response in chronic hepatitis C patients treated with combination therapy of pegylated interferon alpha-2a and ribavirin.

Methods: This is a single-center study including 57 chronic hepatitis C patients who received combination treatments of pegylated interferon alfa-2a and ribavirin. Serum cryoglobulin was detected by cryoprecipitation prior to treatment. Serum hepatitis C virus (HCV) RNA levels were checked before treatment, during the fourth and 12th week of treatment, and during the 24th week after cessation of treatment. The genotype of HCV was determined at baseline. Logistic regression analysis was used to assess the factors associated with sustained virological response.

Results: Twenty-five patients were with MC (43.9%). Twenty-four weeks after cessation of antiviral treatment, sustained virological response achievement in MC(+) patients was significantly lower than that in MC(-) patients (32.0% vs. 75.0%, P = 0.001). Univariate Logistic regression analysis and multivariate Logistic regression analysis found that only MC (odds ratio: 6.375; 95% CI: 1.998- 20.343, P = 0.002) was negatively associated with sustained virological response achievement.

Conclusion: MC is an independent factor negatively associated with sustained virological response in chronic hepatitis C patients treated with pegylated interferon alpha-2a and ribavirin.
View Article and Find Full Text PDF

Download full-text PDF

Source
November 2012

CPred: a web server for predicting viable circular permutations in proteins.

Nucleic Acids Res 2012 Jul 11;40(Web Server issue):W232-7. Epub 2012 Jun 11.

Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 30013, Taiwan.

Circular permutation (CP) is a protein structural rearrangement phenomenon, through which nature allows structural homologs to have different locations of termini and thus varied activities, stabilities and functional properties. It can be applied in many fields of protein research and bioengineering. The limitation of applying CP lies in its technical complexity, high cost and uncertainty of the viability of the resulting protein variants. Not every position in a protein can be used to create a viable circular permutant, but there is still a lack of practical computational tools for evaluating the positional feasibility of CP before costly experiments are carried out. We have previously designed a comprehensive method for predicting viable CP cleavage sites in proteins. In this work, we implement that method into an efficient and user-friendly web server named CPred (CP site predictor), which is supposed to be helpful to promote fundamental researches and biotechnological applications of CP. The CPred is accessible at http://sarst.life.nthu.edu.tw/CPred.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gks529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394280PMC
July 2012
-->