Search

Increasing studies have demonstrated that interferon gamma (IFN-γ), which serves as a critical inflammatory cytokine, is essential to induce the immunosuppressive effects of mesenchymal stem cells (MSCs). However, the mechanisms underlying the enhanced immunosuppressive effects of IFN-γ-stimulated MSCs (γMSCs) are not fully understood. MSC-derived microvesicles (MSC-MVs) have been viewed as potential pivotal mediators of the immunosuppressive effects of MSCs. Moreover, microRNAs (miRNAs) are important regulators of immunological processes and can be shuttled from cell to cell by MVs. The aim of our study was to analyze the the miRNA expression signature of MVs derived from γMSCs (γMSC-MVs), which may provide better understanding of the immunosuppressive property of their parent cells. Through miRNA microarray and bioinformatics analysis, we found 62 significantly differentially expressed miRNAs (DEMs) in γMSC-MVs compared with MSC-MVs. And the potential target genes and signaling pathways regulated by DEMs were predicted and analyzed. Interestingly, many DEMs and predicted signaling pathways had been demonstrated to be involved in immunoregulation. Furthermore, the network between immunoregulation-related pathways and relevant DEMs was constructed. Collectively, our research on the miRNA repertoires of γMSC-MVs not only provides new perspectives into the mechanisms underlying the enhanced immunosuppressive property of γMSCs, but also paves the way to clinical application of these potent organelles in the future.

Our study aimed to identify diffusion-weighted imaging (DWI) parameters obtained from primary nasopharyngeal carcinoma (NPC) at initial presentation, that can predict patients at risk of distant metastases. One hundred and sixty-four patients underwent pretreatment magnetic resonance imaging and DWI. The apparent diffusion coefficient (ADC) mean , ADC skewness , and ADC kurtosis were obtained by histogram analysis. Univariate and multivariate analyses of these ADC parameters together with primary volume (PV), nodal volume (NV), T stage, N stage and presence of locoregional relapse (LRR) were compared between patients with distant metastases (DM+) and patients without distant metastases (DM-) at 5 years using logistic regression. Twenty-eight out of 164 patients (17.1 %) were DM+ (2.5-60 months) and 136/164 patients were DM- (61.2-119.4 months). Compared to DM- patients, the primary tumour of DM+ patients showed significantly lower ADC skewness (ADC values with the greatest frequency were higher) (p = 0.041), and higher PV (p = 0.022), NV (p < 0.01), T stage (p = 0.023), N stage (p < 0.01) and LRR (p < 0.01). On multivariate analysis the ADC skewness was no longer significant (p = 0.120) and only NV and LRR were independent predictors for DM+ (p = 0.023 and 0.021, respectively). DWI showed that compared to DM- patients, DM+ patients had a significantly lower primary tumour ADC skewness , but at initial presentation NV was the only independent predictor of DM.

Neuroinflammation has been suggested to be involved in the pathogenesis of postoperative cognitive dysfunction (POCD). Electroacupuncture (EA) is an irreplaceable method in traditional Chinese medicine that is used for treating neurodegenerative diseases in clinical and experimental studies. The aim of this study was to examine whether EA improves cognitive dysfunction caused by surgery and to investigate the pathological mechanism of TLR2 and TLR4 in the hippocampus of aged rats. A rat model of POCD was established and treated with EA or minocycline. Both EA- and minocycline-treated rats performed significantly better than untreated operated rats in spatial memory tasks of the Morris water maze (MWM) test, spending comparatively greater amounts of time in the target zone during the probe test. Additionally, decreased levels of proinflammatory cytokines (IL-1 β , IL-6, TNF- α , and HMGB1) and decreased TLR2 and TLR4 protein expression in the hippocampus of EA- and minocycline-treated rats were detected. Our data suggested that EA treatment alleviated the cognition performance deficit and neuroinflammation in aged rats following surgery, which may be mediated by inhibiting the expression of hippocampal neuroinflammatory cytokines through the microglia/TLR2/4 pathway.

Mantle cell lymphoma (MCL) remains incurable and new treatments are needed, especially in the relapsed/refractory setting. We therefore investigated the effects of carfilzomib, a novel, long-acting, second-generation proteasome inhibitor, in MCL cells. Eight established MCL cell lines and freshly isolated primary MCL cells were treated with carfilzomib. Cell proliferation was assessed by a 3H-thymidine incorporation assay. Cell apoptosis was evaluated by flow cytometry with annexin V and propidium iodide. Electrophoresis mobility shift (EMSA), Western blot, and luciferase assays were used to analyze NF-κB activation and related signaling proteins. Carfilzomib inhibited growth and induced apoptosis in both established MCL cell lines and freshly isolated primary MCL cells in a dose-dependent manner. In contrast, carfilzomib was less toxic to normal peripheral blood mononuclear cells from healthy individuals. The carfilzomib-induced apoptosis of MCL cells occurred in a caspase-dependent manner through both intrinsic and extrinsic caspase pathways. In addition, carfilzomib inhibited constitutive activation of the NF-κB signaling cascade, both in MCL cell lines and primary MCL cells, by completely blocking the phosphorylation of IκBα. Our results demonstrate that carfilzomib can induce growth arrest and apoptosis in MCL cells and that the mechanism may involve the NF-κB signaling pathway., (© 2017 S. Karger AG, Basel.)

Certain studies have previously indicated that an association may exist between rotavirus infection and primary immune thrombocytopenic purpura (ITP). The present retrospective study aimed to investigate whether rotavirus may cause ITP in children. Firstly, the incidence of ITP in children with or without rotavirus diarrhea was compared. A 14.58% incident rate was observed in children with rotavirus diarrhea compared with a 7.22% incident rate in children without rotavirus diarrhea. Subsequently, the clinical features of ITP children with or without rotavirus infection were compared. The results indicated that ITP children with rotavirus infection were significantly younger, showed significantly decreased mean platelet volume (MPV) levels and presented a significantly higher frequency of bleeding score of 3 against ITP children without rotavirus infection. In conclusion, these findings suggest that rotavirus serves a causative role in ITP.

Autophagy is an evolutionarily conserved catabolic process whereby the cytoplasmic contents of a cell are sequestered within autophagosomes through a lysosome-dependent pathway. Increasing evidence shows that this process is of great importance in a wide range of diseases, including atherosclerosis (AS). Autophagy can be modulated in advanced AS plaques by cytokines, reactive lipids, lipopolysaccharides, advanced glycation end products, and microRNAs. Autophagy exerts both protective and detrimental functions in vascular disorders. However, despite an increasing interest in autophagy, it remains an underestimated and overlooked phenomenon in AS. Therefore, the precise role of autophagy and its relationship with apoptosis need to be described. This review highlights recent findings on the autophagy activities and signaling pathways in endothelial cells, macrophages, and smooth muscle cells that are accompanied by apoptosis in AS. We conclude with recent studies on autophagy modulation as a new therapeutic approach to treat AS.

A series of "turn-on" fluorescence diarylethenes derived from 2,3-bis(2-methylbenzo[b]thiophen-3-yl)-5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-one (1) with alkyl and acetyl substituents were synthesized. The photochemical and photophysical properties of these derivatives, including the photoreaction of crystalline 1, were thoroughly investigated to reveal substituent effects on their properties. The results indicated that alkyl substituents did not significantly affect the absorption and emission spectra of the diarylethenes. However, large absorption and emission wavelength shifts were observed for the diarylethene with an acetyl substituent due to extension of π-π conjugation. Significantly, all of the fluorescent ring-closed forms of the compounds isomerized to their ring-open forms in the presence of Cu(2+) in the dark. EPR results provide clear evidence for the formation of the compound 1 radical cation intermediate that might be generated in the reaction between c-1 and Cu(2+) . DFT calculations found that the ground-state activation energy for ring-opening of 1(.+) was approximately 9.2 kcal mol(-1) lower than that of 1 without Cu(2+) , such that a Cu(2+) -catalyzed oxidative cycloreversion reaction at room temperature might be possible., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease in ageing individuals. Current therapeutic regimen suffers from general side effects and a poor efficiency for PD symptoms. The need for development new therapeutic agents for PD is urgent. Here, we aimed to explore the metabolic mechanism of PD and identified potential novel agents for PD by a sub-pathway-based method. By using the GSE7621 microarray data from the GEO database, we first identified the 1226 differentially expressed genes (DEGs) between PD and normal samples. Then we identified 19 significant enriched metabolic sub-pathways, which may involve in development of PD. Finally, by an integrated analysis of PD-involved sub-pathways and drug-affected sub-pathways, we identified 49 novel small molecular drugs capable to target the PD-involved sub-pathways. Our method could not only identify existing drug (apomorphine) for PD, but also predict potentially novel agents (ketoconazole and astemizole), which might have therapeutic effects via targeting some key enzymes in arachidonic acid metabolism. These candidate agents identified by our approach may provide insights into a novel therapy approach for PD.

Based on a digital micromirror device (DMD) processor as the multi-wavelength narrow-band tunable filter, we demonstrate a multi-port tunable fiber laser through experiments. The key property of this laser is that any lasing wavelength channel from any arbitrary output port can be switched independently over the whole C-band, which is only driven by single DMD chip flexibly. All outputs display an excellent tuning capacity and high consistency in the whole C-band with a 0.02 nm linewidth, 0.055 nm wavelength tuning step, and side-mode suppression ratio greater than 60 dB. Due to the automatic power control and polarization design, the power uniformity of output lasers is less than 0.008 dB and the wavelength fluctuation is below 0.02 nm within 2 h at room temperature.

Background: Cell transplantation of human cord blood mononuclear progenitor cells (HCBMCs) is a new treatment that could restore cardiac functions after acute myocardial infarction (AMI). We hypothesize that multiple doses of HCBMCs might increase homing of transplanted cells to infarcted region, and improve outcome of AMI via inhibition of ischemic-induced inflammatory responses., Methods and Results: HCBMCs were injected intravenously to rabbits that previously underwent ligation of left anterior coronary artery (LAD). Single dose of HCBMCs was intravenously delivered on the 7th day or multiple doses of HCBMCs were delivered on the 7th, 9th, 11th and 13th day after AMI. Homing of HCBMCs was determined by 5-bromodeoxyuridine (BrdU) labeling. The amount of grafted cells homed and retained in the infarcted area was significantly increased in the rabbits that received multiple doses. More viable cardiomyocytes and less collagen deposition were observed also in the group with more injections. Cardiac functions were assessed by echocardiography and hemodynamics. Multiple doses of HCBMCs showed significant benefits in preservation of cardiac functions. In infarcted myocardium, multiple transplantations of HCBMCs showed a significant increase in the myocardial level of anti-inflammatory IL-10 and a marked decrease in the level of the pro-inflammatory IL-6., Conclusions: Multiple injections of HCBMCs markedly increased the amount of grafted cells, beneficially improving cardiac functions after AMI. The findings suggest that multiple doses of HCBMCs might be a novel strategy in the cell therapy for AMI., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

13q deletion syndrome is a rare genetic disorder, especially for group 3 deletion (13q33-q34 deletion). Previously we described a patient with congenital heart defect and mental retardation and proposed that a distal 6Mb region might contain the causative gene of congenital heart defect. Here we present a new patient with congenital heart defects (CHD), hand and foot anomalies and mild mental retardation. We identified a 1.1Mb deletion at chromosome 13q34 with high resolution SNP-array BeadChips (HumanOmni1-Quad, Illumina, USA). This chromosome region contains ten annotated genes, including GRK1, TFDP1, RASA3 and GAS6. To our knowledge, this represents the smallest 13q34 deletion identified to date. Our study provides additional support that distal 13q34 deletion region might contain key gene(s) responsible for cardiac development., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: To explore the effects of compound Danshen dripping pills (CDDP) and CDDP combined with transplantation of human umbilical cord blood cells (HUMNCs) on the inflammatory response, oxidative stress, myocardial cell apoptosis and cardiac function, and also to investigate the possible mechanisms of the combined therapy in the acute myocardial infarction (AMI)., Methods: Rabbit model of AMI successfully established by ligation of the left anterior coronary artery (LAD). Forty rabbits were randomly divided into 4 groups (n=10 per group): a control group, injected with 0.5 mL of saline in 24 h after AMI and then gavaged with 5 mL of saline daily; a CDDP group, injected with saline 0.5 mL after AMI and then gavaged with CDDP (270 mg/d) daily; a transplantation group, injected with 0.5 mL of saline contained 3 × 10(7) HUCBMCs [labeled with green fluorescent protein (GFP)] and then gavaged with 5 mL of saline daily; a combined group, injected with 0.5 mL of saline contained 3 × 10(7) HUCBMCs (labeled with GFP) and then gavaged with CDDP (270 mg/d) daily. Cardiac function index such as left ventricular fractional shorting (LVFS) and ejection fraction(LVEF) were measured by echocardiography; the pathological changes were observed by HE staining and the white blood cells in the myocardium were determined by light microscopy. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in myocardium were detected by nitrotetrazolium blue chloride (NBT) and thiobarbituric acid colorimetric measurement respectively. The number of transplanted cells in the myocardium was examined by GFP positive cells counted with fluorescence microscopy., Results: 1) Compared with the control group (at 1 or 4 week), LVEF and LVFS were significant improved in the CDDP group, the transplantation group and the combined groups (all P<0.05), the improvement degree of cardiac function in the combined group was the most significance. There was no significant difference between the CDDP group and the transplantation group. 2) Compared with the control group (at 1 or 4 week), the number of white blood cell, myocardial cell apoptosis ratio were decreased significantly in the CDDP group, the transplantation group and the combined groups (all P<0.05), this decrease in the combined group was the most significance, and there was no significant difference between the CDDP group and the transplantation group. 3) Compared with control (at 4 week), the SOD activity was increased significantly, and MDA content in myocardium was decreased in the CDDP group, this change in the combined group was the most significance. 4) GFP-positive cells were found to be present in the peri-myocardial infarction area in the transplantation group and the combined group at 1, 4 weeks post-transplantation. The number of the GFP positive cells in the combined group was more than that in the transplantation group (P<0.05)., Conclusion: The intravenous transplantation of HUMNCs combined with the CDDP in the treatment of rabbits with AMI could increase the survival rate of transplanted cells and inhibit the myocardial cell apoptosis, therefore improve the heart function. The possible mechanism of the combined treatment may be involved in the inhibition of the inflammatory response and oxidative stress in the myocardium following AMI.

The aerobic sequencing batch activated sludge system (SBR) was used to remove the toxic and refractory organic pollutant, N,N-dimethylformamide (DMF). The formation property and spatial distribution of the organic toxicity in sludge were studied. The operation parameters were controlled as follows: influent COD was about 300 mg x L(-1), every DMF concentration phase lasted 30 d(40 mg x L(-1), 80 mg x L(-1), 120 mg x L(-1)), the SBR cycle lasted 12 h, and DO was 2.0-3.0 mg x L(-1). The results showed that the sludge toxicity increased in the beginning and then decreased to a steady range at each DMF concentration phase; there was a positive correlation between the sludge toxicity and the initial DMF concentration; most of the sludge organic toxicity was caused by DMF biodegradation and existed in the inner extracellular polymeric substances (EPS) and intracellular section of sludge flocs.

Ischaemia-reperfusion injury (IRI) is the predominant cause of acute kidney injury. Nevertheless, the underlying molecular mechanisms are still unclear. The current study investigated the effects of nicorandil on ATP-sensitive potassium (KATP) channels and the potential signal transduction pathway(s) in a rat kidney IRI model and in cultured tubular HK-2 cells subjected to oxygen and glucose deprivation/reoxygenation (OGD/R) injury. The standard procedure for IRI was performed in newborn rat kidneys. Pretreatment with nicorandil (10 mg/kg) 2 h prior to induction of IRI improved renal function, attenuated tubule damage, and prevented apoptosis of tubule cells, infiltration of neutrophils and macrophages, and production of inflammatory cytokines interleukin (IL)-6, IL-17 and tumour necrosis factor-α. Ischaemia-reperfusion-induced reduction of KIR6.2 was restored to normal levels by nicorandil. The activation of the phosphoinositide-3-kinase (PI3K)-Akt-nuclear factor (NF)-κB axis was detected in this rat kidney IRI model, which was blocked by nicorandil. The renoprotection of nicorandil against IRI was abolished by its inhibitor glibenclamide (1 mg/kg). Similar results were obtained in OGD/R-damaged HK-2 cells. Taken together, our findings demonstrated the specific renoprotective role of nicorandil in the newborn rat IRI kidney by decreasing the production of inflammatory cytokines, and restoring the expression of KIR6.2 potentially through the PI3K-Akt-NF-κB axis.

Objectives: To review degenerative lumbar disease treated with Wallis and the re-herniation cases after the implantation of Wallis, so as to evaluate the effect of the device., Methods: From January 2009 to June 2010, a retrospective analysis was done and 48 patients (30 males and 18 females) with an average age of 43 years (ranging from 17 to 69 years), who received stabilization of the segment using the Wallis device, were reviewed. The involved segments included: 4 cases at L(3-4), 38 cases at L(4-5), 6 cases at L(5)-S(1). Preoperative and postoperative visual analogue scales (VAS) and Oswestry disability index (ODI) were recorded to evaluate the clinical efficiency, imageology diversity was assessed by X-rays and MRI., Results: All cases received fenestration and the implantation of Wallis. No surgery related complications were recorded. There were 48 cases were followed up. The average follow-up period was (20 ± 4) months (12 - 30 months). The average ODI score dropped from 46 ± 10 to 24 ± 7 (t = 12.765, P < 0.05). The average VAS for back and leg pain dropped from 8.1 ± 1.6 to 2.1 ± 1.1(t = 21.881, P < 0.05). Six patients with recurrent lower back and leg pain were diagnosed by MRI, as recurrent herniation (6/48, 12.5%). All re-herniation occurred at L(4-5) level, between 2 and 13 months after the surgery. Three of the 6 patients underwent additional discectomy and fusion, others received conservative treatment., Conclusions: Although existing problems such as recurrence after surgery, the clinical outcome of Wallis in treating protrusion of lumbar intervertebral disc and lumbar stenosis is satisfied in middle-early stage.

Two novel core-extended terrylene diimides on the bay region (CETDIs) were synthesized via annulation of the four additional ethylene units or benzene units on the bay region of the terrylene diimide core. The optical and electrochemical properties of the two compounds were investigated. These CETDIs exhibited broad absorption spectra with high extinction coefficients, which span a wide range in the ultraviolet and visible spectrum from 300 to 700 nm. Furthermore, the redox process of the CETDIs increased from two waves to four waves, and the lowest unoccupied molecular orbital (LUMO) levels were enhanced from -4.00 to -3.59 eV.

The municipal wastewater in China is characterized by low ratio of carbon to nitrogen, which is the key restrictive factor for effective biological removal of nitrogen. In this study, the aerobic-low DO biofilm process was used for the nitrogen removal of municipal wastewater. By means of adjusting inflow ratios of aerobic section to low-DO section, hydraulic retention time (HRT) and inflow ratio of carbon to nitrogen (C/N), the performances of nitrification in aerobic biofilm section and denitrification in low-DO section could be improved, the good performance of nitrogen removal was achieved. In order to insure the good effluent quality, especially for ammonia nitrogen and total nitrogen indexes, the nitrification and denitrification could be made up in aerobic and low-DO biofilm section respectively due to the coexistence of aerobic and anoxic zone in biofilm. There were 3 stages for the research process. In the first stage, the original C/N, inflow ratios of aerobic section to low-DO section were chosen as 3:1 and 1:1 respectively, then the effects of various HRT (aerobic section + low DO section) values such as (10 + 5) h, (8 + 4) h, (6 + 3) h, (4 + 2) h to nitrogen removal were analyzed. According to the conclusion in the first stage, the original C/N was kept at 3:1, HRT (aerobic section + low DO section) was (10 + 5) h. Then, the effects of various inflow ratios to nitrogen removal were studied in the second stage. In the third stage, when HRT(aerobic section + low DO section) was (10 + 5) h and inflow ratio was 1:1, the original C/N were adjusted from 2:1, 3:1, 5:1 to 10:1. To conclude, the optimal parameters for nitrogen removal in the biofilm system were as follows: original C/N = 5:1, inflow ratio of aerobic to low-DO section = 1:1, HRT of aerobic and low-DO sections were 10 h and 5 h respectively. As a result, COD, ammonia nitrogen and total nitrogen could be removed from 254 mg/L to 48 mg/L, 37.2 mg/L to 9.3 mg/L and 48.2 mg/L to 14.8 mg/L respectively.

Data were collected from chronic lymphatic filariasis patients and the public in Yuhang District of Hangzhou. Health status was assessed by using EuroQol (EQ)-5D. A total of 600 questionnaires were sent and 550 (91.7%) returned (276 chronic lymphatic filariasis patients and 274 members of the public). The EQ-SD index score for patients with chronic lymphatic filariasis (0.770 +/- 0.128) were lower than the general public (0.872 +/- 0.073). In contrast to the public (6.6%, 5.8%, 12.0%, 20.4%, and 10.6%), patients reported more problems with their mobility (43.8%), self-care (22.5%), daily activities (44.9%), anxiety/depression (47.8%), and pain/discomfort (29.0%) (P < 0.01). Strength of association were 6.67, 3.86, 3.74, 2.73, and 2.34, respectively. These results indicated that chronic lymphatic filariasis shows an impact on patients' health-related quality of life. It particularly causes great problems in the dimensions of mobility, self-care, and daily activities.

Objective: To determine the genetic diversity of Eucommia ulmoides., Method: 260 samples of 20 populations were analyzed through radom amplified polymorphic DHA (RAPD)., Result: Total polymorphic loci percentage was 96.36 and the average was 38.92. 110 bands were produced with 10 random primers and 106 were polymorphic. Nei's gene diversity (H) was 0.246 1, Shannon's Information index(I) was 0.386 8, Gst was 0.424 4, indicating that 42.44% of the genetic variation was distributed among populations and 57.65% within populations., Conclusion: The genetic variation was relatively high in E. ulmoides, so the genetic diversity conservation principle should mainly focus on protection of the populations.