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Decellularization methodologies have been successfully used in a variety of tissue engineering and regenerative technologies and methods of decellularization have been developed for target tissues and organs of interest. The technology to promote regeneration and functional recovery in the CNS, including brain and spinal cord, has, however, made slow progress mainly because the intrinsic regenerative potential of the CNS is regarded as low. To date, currently available therapies have been unable to provide significant functional recovery and successful therapies, which could provide functional restoration to the injured brain and spinal cord are controversial. In this review, the authors provide a critical analysis, comparing the advantages and limitations of the major decellularization methods and considering the effects of these methods upon the biologic scaffold material. The authors also review studies that supplement decellularized grafts with exogenous factors, such as stem cells and growth factors, to both promote and enhance regeneration through decellularized allografts.

In-stent restenosis (ISR) remains the most common complication of percutaneous coronary intervention. Due to shared risk factors, it is postulated that non-alcoholic fatty liver disease (NAFLD) patients have an increased risk of ISR. This study aimed to determine the association between NAFLD and ISR in patients after bare metal stenting. This study included a cohort of 210 consecutive patients (150 men and 60 women) undergoing follow-up angiography. The primary end-point was angiographic ISR. Multivariate logistic regression analysis was used to identify independent risk factors for ISR. The cumulative ISR rate during follow-up was analyzed by Kaplan-Meier method. Subgroup analyses were also done for different gender. The ISR rate was 29.5%. Patients with NAFLD had a significantly higher prevalence of ISR than patients without NAFLD (43.3 vs. 16.0%, P < 0.001). In logistic regression analysis, NAFLD was associated with increased ISR, independent of low-density lipoprotein cholesterol, body mass index (adjusted odds ratio: 2.688, 95% confidence intervals: 1.285-5.537, P < 0.001). Male NAFLD patients had a higher prevalence of ISR than patients without NAFLD (48.4 vs. 15.3%, P < 0.001), while the prevalence of ISR in female patients with and without NAFLD were comparable (7.7 vs. 17.0%, P = 0.404). Kaplan-Meier analysis showed a significant association between NAFLD and ISR in all patients (log-rank P = 0.008) and in male subgroup (log-rank P = 0.033), but not in female subgroup (log-rank P = 0.313). This preliminary study suggests that NAFLD could independently associate with a high prevalence of ISR, especially in male patients.

Fusarium oxysporum f. sp. cubense (FOC) is the causal agent of banana Fusarium wilt and has become one of the most destructive pathogens threatening the banana production worldwide. However, few genes related to morphogenesis and pathogenicity of this fungal pathogen have been functionally characterized. In this study, we identified and characterized the disrupted gene in a T-DNA insertional mutant (L953) of FOC with significantly reduced virulence on banana plants. The gene disrupted by T-DNA insertion in L953 harbors an open reading frame, which encodes a protein with homology to α-1,6-mannosyltransferase (OCH1) in fungi. The deletion mutants (ΔFoOCH1) of the OCH1 orthologue (FoOCH1) in FOC were impaired in fungal growth, exhibited brighter staining with fluorescein isothiocyanate (FITC)-Concanavalin A, had less cell wall proteins and secreted more proteins into liquid media than the wild type. Furthermore, the mutation or deletion of FoOCH1 led to loss of ability to penetrate cellophane membrane and decline in hyphal attachment and colonization as well as virulence to the banana host. The mutant phenotypes were fully restored by complementation with the wild type FoOCH1 gene. Our data provide a first evidence for the critical role of FoOCH1 in maintenance of cell wall integrity and virulence of F. oxysporum f. sp. cubense.

Women younger than 40 years may face early menopause because of premature ovarian failure (POF). The cause of POF can be idiopathic or iatrogenic, especially the cancer-induced oophorectomy and chemo- or radiation therapy. The current treatments, including hormone replacement therapy (HRT) and cryopreservation techniques, have increased risk of ovarian cancer and may reintroduce malignant cells after autografting. Decellularization technique has been regarded as a novel regenerative medicine strategy for organ replacement, wherein the living cells of an organ are removed, leaving the extracellular matrix (ECM) for cellular seeding. This study aimed to produce a xenogeneic decellularized ovary (D-ovary) scaffold as a platform for ovary regeneration and transplantation. We have developed a novel decellularization protocol for porcine ovary by treatment with physical, chemical, and enzymatic methods. Using hematoxylin and eosin (H&E) staining, DAPI staining, scanning electron microscopy (SEM), and quantitative analysis, this approach proved effective in removing cellular components and preserving ECM. Furthermore, the results of biological safety evaluation demonstrated that the D-ovary tissues were noncytotoxic for rat ovarian cells in vitro and caused only a minimal immunogenic response in vivo. In addition, the D-ovary tissues successfully supported rat granulosa cell penetration ex vivo and showed an improvement in estradiol (E2) hormone secretion.

Objectives Transient elastography (TE), as a non-invasive method, has been studied for evaluation of portal hypertension in patients with chronic liver diseases (CLD) with variable results. We studied the performance of TE for detection of significant portal hypertension, oesophageal varices and large oesophageal varices using meta-analysis. Methods PubMed, the Cochrane Library, EMBASE and ISI web of Knowledge were searched. The studies published in English relating to the diagnostic value of TE for significant portal hypertension, oesophageal varices and large oesophageal varices in patients with CLD were collected. Results A total of 18 studies, which included 3644 patients were analysed. Summary sensitivity and specificity were 0.90 (95% confidence interval (CI), 0.81–0.95) and 0.79 (95% CI, 0.58–0.91) for significant portal hypertension, and 0.87 (95% CI, 0.80–0.92) and 0.53 (95% CI, 0.36–0.69) for oesophageal varices and 0.86 (95% CI, 0.71–0.94) and 0.59 (95% CI, 0.45–0.72) for large oesophageal varices respectively. The HSROCs were 0.93 for significant portal hypertension, 0.84 for oesophageal varices and 0.78 for large oesophageal varices respectively. TE was very informative with 81% probability of correctly detection significant portal hypertension following a ‘positive’ measurement (over the threshold value) and lowering the probability of disease to as low as 11% when ‘negative’ measurement (below the threshold value) when pre-test probability was 50% whereas, for oesophageal varices or large oesophageal varices, the probability of a correct diagnosis following a ‘positive’ measurement did not exceeded 70%. Conclusions TE could be used as a good screening tool for significant portal hypertension, but only moderate diagnostic utility for the prediction of oesophageal varices or large oesophageal varices.

Tumour necrosis factor-α (TNF-α) plays a pivotal role in hepatitis B virus (HBV) clearance and host immune response determining the chronicity of HBV infection. However, studies of the association between TNF-α-857 polymorphism and chronic HBV infection have reported conflicting results. So a meta-analysis was carried out to draw a more precise conclusion. Pubmed (January, 1966-March, 2011) and the China Biological Medicine Database (January, 1978-March, 2011) were searched using the keywords TNF-α gene polymorphism in combination with HBV infection without language restriction. Fourteen studies including 4929 chronic HBV infection cases and 2702 controls describing the C857T genotype were included in the meta-analysis. All fourteen studies focussed on an Asian population. The overall meta-analysis suggested that TNF-α-857T allele reduced the risk of chronic HBV infection in the Asian population (OR = 0.82, 95% CI: 0.71-0.95, P = 0.008) when compared with a spontaneously recovered population. In the sensitivity analyses of the groups obeying Hardy-Weinberg equilibrium (HWE), without the largest study population and without the smallest study population, a similar association was revealed (OR = 0.81, 95% CI: 0.68-0.98, P = 0.043; OR = 0.77, 95% CI: 0.68-0.87, P = 0.0001; OR = 0.81, 95% CI: 0.70-0.95, P = 0.009, respectively). However, when compared with a healthy population, no significant association was found in the Asian population in all groups. So, we draw the conclusion that the TNF-α-857T allele reduces the risk of chronic HBV infection in this Asian population.

Summary. Tumour necrosis factor-α (TNF-α) plays a pivotal role in viral clearance and host immune response to hepatitis B virus (HBV) infection, of which the production capacity in individuals is demonstrated to be influenced by a single nucleotide polymorphism within the promoter region of TNF-α genes. However, there have been conflicting results reported in previous studies on TNF-α-238 and TNF-α-863 gene promoter polymorphisms in chronic HBV infection. To derive a more precise estimation of their relationship, we searched Pubmed (January, 1966–August, 2010) and China Biological Medicine Database (January, 1978–August, 2010) and carried out a meta-analysis involving nineteen studies that included 5245 chronic HBV infection cases and 3181 controls describing G238A genotypes, and eleven studies totalling 3576 cases and 2044 controls describing C863A genotypes. The overall meta-analysis did not suggest significant associations of TNF-α-238 and TNF-α-863 gene promoter polymorphisms with chronic HBV infection. However, in subgroup analysis by ethnicity, it indicated that TNF-α-238A allele carriers (GA + AA) in European populations had an increased risk of developing chronic HBV infection (OR = 2.22, 95% CI: 1.07–4.58, P = 0.032; OR = 4.46, 95% CI: 1.75–11.38, P = 0.002, respectively), when compared with spontaneous recovered and healthy populations, respectively. However, no significant associations were found in Asian populations in all genetic models. So, we draw the conclusion that the TNF-α-238A allele may increase the risk of chronic HBV infection in European populations.

We examined the effect of dendritic cells engineered to express an HBV S antigen CD40L fusion gene (HBV S-ecdCD40L). The DNA of HBV S gene and the cDNA of the extracellular domain of human CD40 ligand were linked by cloning. Peripheral blood mononuclear cells (PBMC) from healthy adults were incubated and induced into dendritic cells (DC) in presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4(IL-4). The DCs were transfected the novel construct, and the impact of the expressed clone assessed. We find that, compared with control groups, modification of DCs with HBV S-ecdCD40L fusion gene resulted in the activation of DCs with upregulated expression of immunologically important cell surface molecules (CD80, CD86 and HLA-DR) and proinflammatory cytokines (IL-12). The DCs modified with HBV S-ecdCD40L are able to stimulate enhanced allogeneic T-cell proliferation in vitro. Thus, the fusion gene HBV S-ecdCD40L can promote DC's activation and enhance its function and may prove to be the foundation for a new type of hepatitis B vaccine.

In the title compound, [Mn(C8H4O4)(C19H12N4O)2]n or [Mn(1,4-BDC)(L)2]n, where 1,4-BDC is the benzene-1,4-dicarboxyl­ate dianion and L is 4-(1H-1,3,7,8-tetra­azacyclo­penta­[l]phenanthren-2-yl)phenol, the MnII atom is six-coordinated by two bidentate L and two monodentate 1,4-BDC ligands, resulting in a distorted trans-MnO2N4 octa­hedral geometry. The MnII atoms are bridged by the 1,4-BDC ligands, forming a single-chain polymer structure. In addition, neighboring single chains inter­act through π–π inter­actions, generating a two-dimensional network. Mn has site symmetry \overline{1}; the complete 1,4-BDC unit is also built up by inversion symmetry.

To investigate the effects of angiotensin converting enzyme inhibitor (ACEI) captopril on Calpain-mediated cardiomyocytes apoptosis and cardiac function in diabetic rats.Thirty adult male SD rats were randomly divided into 3 groups (n = 10), normal control group (NC group), diabetes mellitus group (DM group)and captopril treated group (Cap group). Streptozocin (STZ) were used to make the model of diabetes mellitus, captopril was administrated by gavage at the dose of 50 mg/kg every day, while in NC group and DM group the same volume of normal saline was administrated. Twelve weeks later, left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVDEP), maximal rise rate of left ventricular pressure (+ dp/dtmax) and maximal fall rate of left ventricular pressure (- dp/dtmax) were detected; Western blot was used to detect the expression of Calpain-1 Calpain-2, Bcl-2, Bax and total Caspase3 protein; apoptosis index (AI) were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL).Compared with NC group, LVDEP was significantly higher; LVSP, + dp/dtmax and - dp/dtmax were significantly decreased (P0.05); Bcl-2 protein expression was decreased; the expression of Calpain-1, Calpain-2, Bax and total Caspase3 protein were increased; the value of AI was significantly increased. Compared with DM group, LVDEP was significantly lower; LVSP, + dp/dtmax and - dp/dtmax were significantly increased (P0.05); Bcl-2 protein expression was increased, the expression of Calpain-1, Calpain-2, Bax and total Caspase3 protein were decreased; the value of AI was significantly decreased (P0.05).Captopril can protect diabetic myocardial structure through inhibiting activation of Calpain-1 and Calpain-2, up-regulating the expression of Bcl-2, down-regulating the expression of Bax to inhibit Caspase3 dependent apoptosis, thereby improving the ventricular function and myocardial structure.

Nonalcoholic fatty liver disease (NAFLD) has been suggested to be a strong risk factor of colorectal benign adenomas and advanced neoplasms. The aim of this large cohort study was to further investigate the prevalence of colorectal malignant neoplasm (CRMN) in patients with NAFLD and determine whether association between NAFLD and CRMN exists. 2,315 community subjects (1,370 males and 945 females) who underwent a routine colonoscopy according to international colorectal cancer screening guideline were recruited. Nature of colorectal lesions determined by biopsy and NAFLD was diagnosed by ultrasound. Binary logistic regression analysis was applied to explore the related associations. Prevalence of CRMN was 29.3 % (77/263) in patients with NAFLD, which was significantly higher than 18.0 % (369/2,052) in the control group (P < 0.05). In addition, malignant neoplasm in NAFLD group occurred more frequently at sigmoid colon than in control group (14.3 vs. 11.9 %). The incidence of highly-differentiated colorectal adenocarcinoma in NAFLD group was significantly higher than control group (62.3 vs. 9.8 %). Univariate analysis showed that NAFLD had strong association with CRMN (OR 2.043; 95 % CI 1.512–2.761; P < 0.05). After adjusting for metabolic and other confounding factors, NAFLD remained as an independent risk factor for CRMN (OR 1.868; 95 % CI 1.360–2.567; P < 0.05). NAFLD was an independent risk factor for CRMN. Sigmoid carcinoma and highly differentiated colorectal adenocarcinoma were more commonly found in NAFLD. (ClinicalTrials.gov number, NCT01657773, website: http://clinicaltrials.gov/ct2/show/NCT01657773?term=zheng+minghua&rank=1).

There are accurate but inconclusive data on the association between single nucleotide polymorphisms (SNPs) of interleukin (IL)-28B and sustained virological response (SVR) in chronic hepatitis C (CHC). This meta-analysis aimed to derive a more precise estimation of the effects of IL-28B SNPs locus (rs12979860 and rs8099917) on SVR in naive CHC patients receiving pegylated interferon alpha (PEG-IFN-α) plus ribavirin. Literature search was conducted up to June, 2011, in PubMed, EMBASE and Cochrane Database of Systematic Reviews. A total of 36 studies involving 10912 cases with CHC receiving PEG-IFN-α plus ribavirin met the inclusion criteria. Analyses were stratified either by ethnicity or genotype of hepatitis C virus. In genotype 1/4 patients, rs12979860 CC was associated with high SVR in CHC patients (Caucasian: odds ratio (OR), 4.567; 95% confidence interval (CI), 3.826–5.452; Asian: OR, 4.033; 95%CI, 3.050–5.333; African American: OR, 4.297; 95%CI, 2.168–8.515; Hispanics: OR, 4.350; 95%CI, 2.817–6.717) but had no effect in genotype 2/3. In Caucasian (genotype 1/4: OR, 2.542; 95%CI, 2.108–3.065; genotype 2/3: OR, 1.363; 95%CI, 1.020–1.820) and Asian (genotype 1/4: OR, 5.214; 95%CI, 3.694–7.360; genotype 2/3: OR, 1.785; 95%CI, 1.095–2.910), rs8099917 TT was associated with high SVR in both genotype 1/4 and 2/3. Meta-regression showed that in Caucasians with CHC genotype 1/4, gender male might contribute to the effect of rs12979860 on SVR but advanced fibrosis might weaken this effect. Furthermore, in Asians with CHC genotype 1/4, high baseline viral load and advanced fibrosis might also undermine the effect of rs8099917 on SVR. This meta-analysis suggested that IL-28B rs12979860 CC and rs8099917 TT were associated with high SVR rate in CHC genotype 1/4. In CHC genotype 2/3, rs8099917 TT carriers also had higher SVR.

Background and objectivesSerum alanine aminotransferase (ALT) activity is the most common tool for the assessment of liver diseases. However, it is not clear whether the current normal ALT range really discriminate patients with or without liver diseases. The present study was to establish a new normal range of ALT and examine its ability to identify patients with hepatitis B or nonalcoholic fatty liver disease (NAFLD) in Chinese Han population.Methods53037 adults were included in this study from January 1st 2008 to August 31st 2010. The 95th percentile of ALT in population with relative low risk factors for liver diseases was set as the new upper limits of normal ALT in gender-specific manner.ResultsThe 95(th) percentile levels at low risk factors for liver diseases were achieved at 35 U/L for men and 23 U/L for women. The concordance statistics for detection were 0.873 (95%CI: 0.865-0.881) for HBV and 0.932 (95%CI: 0.927-0.937) for NAFLD in men while 0.857 (95%CI: 0.850-0.864) for HBV and 0.909 (95%CI: 0.903-0.915) for NAFLD in women. The median sensitivity of the current used ALT upper limit (40 U/L) was 6.6% for HBV and 29.7% for NAFLD and median specificity was 98.7% for men and 99.4% for women. Using our new-derived thresholds, the sensitivities ranged from 35.3% to 61.1% and the specificities were 94.8% for men and 94.6% for women.ConclusionsOur results suggest that upper limits of ALT 35 U/L for men and 23 U/L for women in Chinese Han population. Re-consideration of normal limits of ALT should be recommended.Trial registrationChiCTR.org ChiCTR-OCS-11001173.

Risk stratification for spontaneous bacterial peritonitis (SBP) in patients with cirrhosis and ascites helps guide care. Existing prediction models, such as end-stage liver disease (MELD) score, are accurate but controversial in clinical practice. We developed and validated a practical user-friendly bedside tool for SBP risk stratification of patients with cirrhosis and ascites. Using classification and regression tree (CART) analysis, a model was developed for prediction of SBP in cirrhosis with ascites. The CART model was derived on data collected from 676 patients admitted from January 2007 to December 2009 retrospectively, and then was prospectively tested in another independent 198 inpatients between January 2010 and December 2010. The accuracy of CART model was evaluated using the area under the receiver operating characteristic curve. The performance of the model was further validated by comparing its predictive accuracy with that of the MELD score. Furthermore, the model was used to stratify SBP among patients with MELD scores under 15. CART analysis identified four variables for prediction of SBP: creatinine, total bilirubin, prothrombin time and white blood cell count, and three risk groups: low (2.0%), intermediate (27.5–33.3%) and high (60.6–86.4%) risk. The accuracy of CART model (0.881) exceeded that of MELD (0.791). Subjects in the intermediate risk and high risk groups had 22.21-fold (95% confident interval (CI), 9.98–49.45) and 173.50-fold (95% CI, 77.68–634.33) increased risk of SBP, respectively, comparing with the low risk group. Similar results were found when this risk stratification was applied to the validation cohort. Cirrhotic patients with ascites at low, intermediate, and high risk for SBP can be easily identified using CART model, which provides clinicians with a validated, practical bedside tool for SBP risk stratification.

The title compound, {[Zn(HIDC)(H2O)]·0.5H2O}n (HIDC2− is the imidazole-4,5-dicarboxyl­ate dianion, C5H2N2O4), exists as a one-dimensional coordination polymer formed by HIDC2− ligands bridging ZnII atoms, with a Zn⋯Zn separation of 6.156 (2) A. The ZnII ion exists in a distorted square-pyramidal coordination, involving two N and two O atoms from two symmetry-related bidentate HIDC2− groups, and one water mol­ecule.

The title complex, [Hg2Br4(C7H16S2)]n, has a chain structure. Two bridging Br atoms and two terminal Br atoms coordinate to two HgII atoms, forming an (HgBr2)2 dimer, which is located on an inversion center. The 1,3-bis(ethylsulfanyl)propane ligands, which lie on a twofold axis, bridge the (HgBr2)2 dimers, forming a one-dimensional chain. The HgII atom adopts a tetrahedral geometry, formed by three Br and one S atoms.