[Effect of different parts of Pinelliae Rhizoma Decoction against airway inflammation and analysis of effective components].

This study investigated the material basis and mechanism of Pinelliae Rhizoma Decoction in the treatment of airway inflammation. The cigarette smoke combined with lipopolysaccharide(LPS) was used to induce an airway inflammation model in mice. The expression levels of IL-6 and IL-8 in the bronchoalveolar lavage fluid(BALF) and the phosphorylation levels of p38 and IκB in the lungs of mice were taken as indexes to screen the effective extracts by system solvent extraction from Pinelliae Rhizoma Decoction(dichloromethane extract, ethyl acetate extract, n-butanol extract, etc.). Meanwhile, the human bronchial epithelial(16-HBE) cell model of cigarette smoke extract(CSE)-induced injury was established, and the mRNA expression levels of IL-6 and IL-8 and the phosphorylation levels of p38 and IκB proteins were also taken as indexes to evaluate the anti-inflammatory effect of different extracts of Pinelliae Rhizoma Decoction. The results showed that Pinelliae Rhizoma Decoction significantly antagonized airway inflammation in mice by down-regulating the expression levels of IL-6 and IL-8 in mice with airway inflammation and 16-HBE cells with CSE-induced injury and inhibiting the phosphorylation levels of p38 and IκB. The dichloromethane and ethyl acetate extracts of Pinelliae Rhizoma Decoction showed significant anti-inflammatory effects, while such effects of other extracts were not prominent. Furthermore, the database of Pinelliae Rhizoma composition was constructed, and the components in effective extracts were analyzed by HPLC-TOF-MS and Nano-LC-MS/MS. As revealed by the results, the compositions of the two effective extracts were similar with 36 common components. They were combined and then divided into Pinelliae Rhizoma alkaloids(PTAs) and Pinelliae Rhizoma non-alkaloids(PTNAs) by 732 cation-exchange resin. Further in vitro investigation confirmed the significant anti-inflammatory effect of PTNAs, while such effect of PTAs was not manifest. The MS analysis showed 172 peptides and 7 organic acids in PTNAs. The peptide content in PTNAs was 63.5% measured by quantitative analysis of BCA assay, and the organic acid content was 9.92% by potentiometric titration method. The findings of this study suggested that Pinelliae Rhizoma Decoction could antagonize airway inflammation in mice by inhibiting phosphorylation of p38 and IκB and blocking the activation of MAPK and NF-κB signaling pathways, and the effective components were related to the peptides and organic acids in PTNAs. The above results lay a foundation for the research on the mechanism and material basis of Pinelliae Rhizoma in antagonizing airway inflammation.

In vivo MRI detection of carotid atherosclerotic lesions and kidney inflammation in ApoE-deficient mice by using LOX-1 targeted iron nanoparticles.

Lectin-like Oxidized Low-Density Lipoprotein Receptor 1 (LOX-1) plays a key role in atherosclerotic plaque initiation, formation and rupture, as well as in hyperlipidemia-induced glomerular disease. Here we report a sensitive, specific and biocompatible LOX-1-targeted-USPIO for the noninvasive MR imaging of LOX-1 within carotid atherosclerotic lesions and glomerular disease in apoE-deficient mice. In vitro analysis showed the highest uptake of targeted USPIOs in only activated RAW264.7 macrophages, and in vivo MRI studies showed signal loss in carotid atherosclerotic lesions after administration of targeted USPIOs at 8h and 24h. These areas of signal loss were correlated with the presence of nanoparticles in the atherosclerotic lesions, and immunohistochemistry and Perl's staining confirmed the co-localization of the LOX-1/macrophages/MMP-9 and targeted nanoparticles. Finally, additional studies suggest that this targeted probe may have potential to noninvasively image early glomerular disease. This finding may provide important methods for characterizing vulnerable atherosclerotic plaques and hyperlipidemia-induced glomerular diseases. FROM THE CLINICAL EDITOR: A functionalized USPIO-based negative contrast material was used in this study, demonstrating feasibility of sensitive MRI-based detection of atherosclerotic plaque formation in the carotid arteries and in the renal cortex, paving the way to potential future clinical applications.

Synthesis and Biological Activities of Oxazolidinone Pleuromutilin Derivatives as a Potent Anti-MRSA Agent.

A series of pleuromutilin derivatives containing an oxazolidinone skeleton were synthesized and evaluated in vitro and in vivo as antibacterial agents. Most of the synthesized derivatives exhibited potent antibacterial activities against three strains of Staphylococcus aureus (including MRSA ATCC 33591, MRSA ATCC 43300, and MSSA ATCC 29213) and two strains of Staphylococcus epidermidis (including MRSE ATCC 51625 and MSSE ATCC 12228). Compound 28 was the most active antibacterial agent in vitro (MIC = 0.008-0.125 µg·mL-1) and exhibited a significant bactericidal effect, low cytotoxicity, and weak inhibition (IC50 = 20.66 µmol·L-1) for CYP3A4, as well as exhibited less possibility to cause bacterial resistance. Furthermore, in vivo activities indicated that the compound was effective in reducing MRSA load in a murine thigh infection model. Moreover, it clearly facilitated the healing of MRSA skin infection and inhibited the secretion of the TNF-α, IL-6, and MCP-1 inflammatory factors in serum. These results suggest that oxazolidinone pleuromutilin is a promising therapeutic candidate for drug-resistant bacterial infections.

Biodegradable PTX-PLGA-coated magnesium stent for benign esophageal stricture: An experimental study.

Biodegradable stents can degrade step by step and thereby avoid secondary removal by endoscopic procedures in contrast to metal stents. Herein, a biodegradable composite stent, a magnesium (Mg)-based braided stent with a surface coating of poly (lactic-co-glycolic acid) (PLGA) containing paclitaxel (PTX), was designed and tested. By adding this drug-loaded polymer coating, the radial force of the stent increased from 33 Newton (N) to 83 N. PTX was continuously released as the stent degraded, and the in vitro cumulative drug release in phosphate-buffered saline for 28 days was 115 ± 13.5 µg/mL at pH = 7.4 and 176 ± 12 µg/mL at pH = 4.0. There was no statistically significant difference in the viability of fibroblasts of stent extracts with different concentration gradients (P > 0.05), while the PTX-loaded stents effectively promoted fibroblast apoptosis. In the animal experiment, the stents were able to maintain esophageal patency during the 3-week follow-up and to reduce the infiltration of inflammatory cells and the amount of fibrous tissue. These results showed that the PTX-PLGA-coated Mg stent has the potential to be a safe and effective approach for benign esophageal stricture. STATEMENT OF SIGNIFICANCE: We designed a biodegradable composite stent, having poly (lactic-co-glycolic acid) (PLGA) containing paclitaxel (PTX) coated the surface of the magnesium (Mg)-based braided stent. We evaluated in vitro and in vivo characteristics of the Mg esophageal stent having a PLGA coating plus a variable concentration of PTX in comparison with the absence of PTX PLGA coating. The PTX PLGA stents exerted higher radial force than stents without coating, degraded more quickly in an acid medium, and effectively promoted fibroblast apoptosis in vitro experiments. In a rabbit model of caustic-induced esophageal stricture, there was an increased lumen and decreased inflammation of the esophageal wall in the animals stented with PTX-PLGA versus the sham group, indicating a potential approach for benign esophageal stricture.

Possible role for the thioredoxin system in the protective effects of probucol in the pancreatic islets of diabetic rats.

1. Probucol, a lipid-lowering agent with a potent anti-oxidant action, protects diabetic pancreatic islets by an as yet unknown mechanism. Thioredoxin-interacting protein (TXNIP), an endogenous inhibitor of the ubiquitous thiol oxidoreductase thioredoxin (TRX), has been associated with oxidative stress in diabetic rat islets. The aim of the present study was to examine the effects of probucol on diabetic islet function and expression of TRX and TXNIP. 2. Thirty rats were randomly assigned to one of three groups: a normal control group, a diabetic group and a probucol-treated diabetic group. After 8 weeks treatment with probucol (500 mg/kg per day), plasma malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) activity were determined using chemical colourimetric methods. In addition, the expression of insulin, TRX and TXNIP in islets was analysed using immunohistochemical, western blot and reverse transcription-polymerase chain reaction methods. 3. The expression of TRX and insulin in islets and plasma SOD and CAT activity were lower, but the expression of TXNIP in islets and plasma MDA were higher, in diabetic compared with normal control rats. Upregulated expression of TRX and insulin and downregulated expression of TXNIP were observed in probucol-treated diabetic rats. Probucol treatment increased plasma SOD, decreased plasma MDA and improved hypoinsulinaemia in diabetic rats. 4. The results indicate that treatment with probucol decreases TXNIP expression and increases TRX expression, which may alleviate hypoinsulinaemia by reducing oxidative stress. Therefore, probucol shows promise as a supplemental therapy for islet protection in Type 2 diabetes mellitus.

[Effects of Radix Astragali on IL-1beta, TNF-alpha and antigen expression of peripheral blood mononuclear cells in patients with Graves disease].

OBJECTIVE: To study the effects of Radix Astragali on serum cytokines IL-1beta, TNFalpha and antigen expression of peripheral blood mononuclear cells (PBMCs) in patients with Graves disease (GD). METHODS: Eighty GD patients at their first visit were randomly assigned to the methimazole (MMI) group (Group A) and the MMI combined Radix Astragali group (Group B), 40 in each. The improvement of clinical symptoms and thyroid functions were observed after one-month treatment. The serum IL-1beta and TNF-alpha levels in the peripheral blood were determined using radioimmunoassay. The expression levels of surface antigen CD80, CD54, and HLA-DR of PBMCs were detected using flow cytometry. RESULTS: The improvement of the thyroid gland function was similar in the two groups. There was no obvious change in the levels of autoantibody TGAb or TPOAb of the two groups. Symptoms such as fear of heat, hidrosis, palpitation, and so on were more obviously improved in Group B than in Group A (P < 0.05). The serum IL-betaP, TNFalphaa, CD00 levels in the peripheral blood were all improved in the two groups after treatment when compared with before treatment ( P < 0.05 or P < 0.01). But the serum levels of IL-beta and TNFalpha decreased more obviously in Group B than in Group A ( P < 0.05). The expression of CD54 decreased more obviously in Group B (P < 0.01), showing statistical difference when compared with Group A at the same time point (P < 0.05). CONCLUSION: Radix Astragali could significantly relieve the clinical symptoms such as hidrosis and palpitation, regulate the immune function of GD patients, playing an important role in the adjuvant therapy for GD.

Abnormalities of the PRMT1-ADMA-DDAH1 metabolism axis and probucol treatment in diabetic patients and diabetic rats.

BACKGROUND: Symmetrical dimethylarginine (ADMA) endogenously inhibits nitric oxide synthase (NOS) and strongly indicates oxidant stress, whose formation primarily derived from type 1 protein arginine N-methyltransferase (PRMT1) and whose metabolism was governed by type 1 dimethylarginine dimethylaminohydrolase (DDAH1). This study aimed to evaluate participation of the PRMT1-ADMA-DDAH1 metabolism axis in the kidneys of type 2 diabetes model rats and human subjects, and the effect of probucol on this axis and renal function. METHODS: A total of 30 rats were randomly assigned to a normal group (NC, n=10), diabetic group (DM, n=10), and a diabetics under probucol treatment group (PM, n=10). Throughout 8 weeks of probucol treatment, plasma NOS, the malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), and catalase (CAT) activity were evaluated by chemical colorimetric approach. ADMA concentration was evaluated with an enzyme-linked immunosorbent assay (ELISA) and analysis of expression of PRMT1 and DDAH1 in kidneys with reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry (IHC) and western blotting were performed. RESULTS: The expression of DDAH1 in the kidney, and the plasma NOS, NO, SOD, and CAT activities in diabetic group were lower, while MDA and the expression of PRMT1 and ADMA were higher in contrast to the control group. In diabetics rats receiving probucol, the expressions of DDAH1 and ADMA were downregulated, whereas that of PRMT1 was upregulated. Probucol inhibited the indexes of oxidative stress and improved the kidney function in both diabetic rats and humans. CONCLUSIONS: We found that the expression of the PRMT1-ADMA-DDAH1 axis was altered in the kidneys of diabetic rats. Moreover, results indicated that probucol therapy regulates expression at both ends of this axis, which may preserve renal function by reducing oxidant stress. Therefore, probucol may partially restore expression of the PRMT1-ADMA-DDAH1 axis in diabetic kidneys, immigrate oxidant stress, and enhance renal function.

Mesencephalic astrocyte-derived neurotrophic factor ameliorates steatosis in HepG2 cells by regulating hepatic lipid metabolism.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a global metabolism-associated liver disease. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a newly discovered secreted protein that is involved in metabolic homeostasis. However, much remains to be discovered about its function in hepatic lipid metabolism; thus, we assessed whether MANF could regulate hepatic metabolism. AIM: To establish in vivo and in vitro NAFLD models to explore the role of MANF in hepatic lipid metabolism. METHODS: HepG2 cells treated with free fatty acids (FFAs) and ob/ob mice were used as NAFLD models. Liver tissues collected from wild type and ob/ob mice were used to detect MANF expression. Cells were treated with FFAs for different durations. Moreover, we used lentiviral constructs to establish overexpression and knockdown cell models in order to interfere with MANF expression levels and observe whether MANF influences hepatic steatosis. Western blot analysis and quantitative real-time PCR were used to detect protein and gene expression, and oil red O staining was used to visualize intracellular lipid droplets. RESULTS: Hepatic MANF protein and mRNA expression in wild type mice were 10-fold and 2-fold higher, respectively, than those in ob/ob mice. The MANF protein was temporarily increased by 1.3-fold after stimulation with FFAs for 24 h and gradually decreased to 0.66-fold that of the control at the 72 h time point in HepG2 cells. MANF deficiency upregulated the expression of genes involved in fatty acid synthesis, cholesterol synthesis, and fatty acid uptake and aggravated HepG2 cell steatosis, while MANF overexpression inhibited fatty acid synthesis and uptake and cholesterol synthesis, and rescued HepG2 cells from FFAs-induced steatosis. Furthermore, a significant decrease in triglyceride levels was observed in the MANF overexpression group compared with the control group (0.4288 ± 0.0081 mmol/g vs 0.3746 ± 0.0121 mmol/g, P < 0.05) upon FFAs treatment. There was also a 17% decrease in intracellular total cholesterol levels between the MANF overexpression group and the control group (0.1301 ± 0.0059 mmol/g vs 0.1088 ± 0.0009 mmol/g, P < 0.05) upon FFAs treatment. Moreover, MANF suppressed lipid deposition in HepG2 cells. CONCLUSION: Our findings indicate that MANF improves the phenotype of liver cell steatosis and may be a potential therapeutic target in hepatic steatosis processes.

Synthesis and antimultidrug resistance evaluation of icariin and its derivatives.

A series of icariin derivatives were synthesized. Their multidrug resistance (MDR) reversal activities were evaluated by MTT assay and the results indicated that the derivatives were the potent modulators of MDR. It was showed that the derivatives significantly increased the intracellular accumulation of ADR in MCF-7/ADR cells compared with drug sensitive MCF-7 cells. The results of bi-directional assay and reverse transcription polymerase chain reaction (RT-PCR) assay showed that the derivatives had high inhibitory activity against P-gp efflux function and significantly down-regulated on the expression of P-gp.

Angiotensin-converting enzyme inhibitors improve hepatic steatosis by modulating expression of tumour necrosis factor-alpha, interleukin-6 and adiponectin receptor-2 in rats with type 2 diabetes.

1. Angiotensin-converting enzyme inhibitors (ACEI) are hypotensive drugs that have been shown to prevent Type 2 diabetes mellitus (T2DM) in high-risk individuals. However, in T2DM, the effects of ACEI on hepatic steatosis are not known. The aim of the present study was to examine the effects of ACEI on changes in liver histology and hepatic mRNA expression of adipokines in rats with T2DM. 2. Thirty-six rats were divided into a normal control group, a T2DM group and a fosinopril-treated group. After six weeks of treatment with 5 mg/kg per day fosinopril, an ACEI, changes in liver histology, serum fasting glucose (FG), insulin, triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, adiponectin were evaluated, as was hepatic TNF-alpha, IL-6 and adiponectin receptor-2 (adipoR2) mRNA expression. 3. The degree of hepatic steatosis and inflammation, serum FG, insulin, TG, TC, ALT, TNF-alpha and IL-6 concentrations and hepatic TNF-alpha and IL-6 mRNA expression were significantly higher in rats with T2DM than in normal controls. Serum adiponectin concentrations and hepatic adipoR2 mRNA expression in rats with T2DM were significantly lower than in normal controls. Fosinopril significantly reduced the degree of hepatic steatosis, serum FG, insulin, ALT, TNF-alpha and IL-6 concentrations and hepatic TNF-alpha and IL-6 mRNA expression. Fosinopril significantly increased serum adiponectin concentrations and hepatic adipoR2 mRNA expression. 4. In conclusion, the ACEI improved insulin sensitivity and hepatic steatosis in rats with T2DM by increasing circulating adiponectin and hepatic adipoR2 levels, in addition to reducing pro-inflammatory cytokine levels in the circulation and liver.

[Characterization Composition of Soluble Microbial Products in an Aerobic Granular Sludge System].

Using flocculent activated sludge as seed sludge to cultivate aerobic granular sludge in a SBR, the main objective of this study was focused on the accumulation, relative molecular mass distribution, and composition of soluble microbial products (SMP) in an aerobic granular sludge (AGS) system. SMP were predominant (71-85 mg·L-1) in the effluent of the AGS system. The formation of SMP was related to substrate utilization, biomass decay, and EPS hydrolysis. A relative molecular mass distribution analysis indicated that the majority of SMP, accounting for about 54.8%-71.7%, had Mr<3×103; whereas, the Mr>100×103 formed a small fraction, constituting only 9.3%-14.5%. Three-dimensional excitation emission matrix fluorescence spectra (3D-EEM) identified four peaks in SMP, belonging to aromatic protein-like, tryptophan protein-like, humic acid-like, and fulvic acid-like substances. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that esters (39.0%), short chain alkanes (14.9%), alkenes (11.7%), and alcohols (7.6%) were the main compounds in SMP. Most notably, bis(2-ethylhexyl) phthalate, as one kind of ester, accounted for 32% of the identified SMP.

Targeting Early Apoptosis in Acute Ischemic Stroke with a Small-Molecule Probe.

Inhibiting apoptotic cells helps ameliorate ischemic injury. Actually, only the apoptotic cells in early stage could be rescued. Molecular imaging of the early apoptosis would make sense in ischemic stroke; however, few of apoptosis molecular probes could specifically target early apoptosis. This study developed a small-molecule early apoptosis targeting probe CYS-F, which was synthesized by cystine with fluorescein isothiocyanate dyes. And the final molecular weight of CYS-F was only 1013 Da, which was much smaller than the traditional apoptosis marker annexin V. CYS-F showed excellent early apoptosis targeting ability both in vitro and in vivo. And CYS-F was cleared rapidly from the circulation with a blood half-life of 1.325 h. A favorable match was obtained between the images in fluorescence imaging and magnetic resonance imaging in stroke models. The target-to-background ratio of the lesions on 0 h was negative, which reflected the decreased blood flow. Multimodal molecular imaging showed the therapeutic effect of cystamine was dose dependence and CYS-F could also predict the outcome of ischemic stroke at an early stage. The versatility of CYS-F provides a comprehensive and convenient route for clinical decision-making in acute ischemic stroke.

Association between NR5A2 and the risk of pancreatic cancer, especially among Caucasians: a meta-analysis of case-control studies.

BACKGROUND: Previous studies have reported that nuclear receptor subfamily 5, group A, member 2 (NR5A2) polymorphisms (rs3790843 G>A, rs3790844 T>C, rs12029406 C>T) are associated with the risk of pancreatic cancer. However, the results of epidemiological investigations are still controversial. In order to explore its potential attributing factors, we pooled the updated literatures to evaluate the association between NR5A2 polymorphism and the risk of pancreatic cancer in this meta-analysis. MATERIALS AND METHODS: Databases such as PubMed, Google Scholar and China National Knowledge Infrastructure were searched for eligible articles following strict inclusion and exclusion criteria (updated to November 18, 2017). Odds ratios (ORs) and 95% CIs were computed to assess the intensity of association. In addition, heterogeneity, sensitivity analysis and publication bias were explored. All statistical analyses were conducted by STATA 14.0. RESULTS: Our results showed that the rs3790843 (GA vs GG: OR=0.86, CI=0.76-0.98, P=0.992; GA+AA vs GG: OR=0.83, CI=0.73-0.94, P=0.950; A vs G: OR=0.85, CI=0.78-0.93, P=0.802), rs3790844 (CC vs TT: OR=0.65, CI=0.54-0.78, P=0.617; CC vs TT+CT: OR=0.73, CI=0.62-0.85, P=0.742; C vs T: OR=0.78, CI=0.73-0.84, P=0.555) and rs12029406 (TT vs CC: OR=0.73, CI=0.61-0.89, P=0.483; TT vs CC+CT: OR=0.78, CI=0.66-0.92, P=0.648; T vs C: OR=0.87, CI=0.79-0.95, P=0.837) polymorphisms were associated statistically with the risk of pancreatic cancer. Furthermore, the results of subgroup analysis showed that rs3790843 and rs3790844 polymorphisms were especially related to the risk of pancreatic cancer in Caucasian population. CONCLUSION: Our results revealed that NR5A2 may have a protective effect on pancreatic cancer. However, more well-designed researches are needed to verify the relationship between NR5A2 polymorphisms and the risk of pancreatic cancer.

Association between ERCC2 Lys751Gln polymorphism and the risk of pancreatic cancer, especially among Asians: evidence from a meta-analysis.

Single nucleotide polymorphisms (SNPs) of Excision repair cross-complementing group 2 (ERCC2) gene are suspected to affect the risk of pancreatic cancer. Many studies have reported the association between ERCC2 Lys751Gln polymorphism (rs13181) and the susceptibility to pancreatic cancer, but the outcomes remained controversial. To comprehensively determine this association, we conducted a meta-analysis based on a total of eight studies. Evidence for this association was obtained from the PubMed, EMBASE, Web of Science and Chinese National Knowledge Infrastructure (CNKI) databases. In general, a significant association was found between ERCC2 rs13181 polymorphism and the susceptibility to pancreatic cancer in four genetic models [CC vs. AA: OR = 1.56, (95% CI: 1.28-1.90), P = 0.470; AC/CC vs. AA: OR=1.20, (95% CI: 1.06-1.36), P = 0.396; CC vs. AC/CC: OR = 1.50; (95% CI: 1.24-1.81), P = 0.530; C vs. A: OR=1.22, (95%CI:1.11-1.34), P = 0.159]. Furthermore, stratified analyses by ethnicity indicated a significant association only in the Asian population. Our results indicate that the ERCC2 Lys751Gln polymorphism might be important in stimulating the development of pancreatic cancer, especially for Asians.

Yin Yang-1 suppresses pancreatic ductal adenocarcinoma cell proliferation and tumor growth by regulating SOX2OT-SOX2 axis.

The transcription regulator Yin Yang-1 (YY1) serves as a tumor suppressor in pancreatic ductal adenocarcinoma (PDAC). However, the function of YY1 in proliferation of PDAC cells remains to be clarified. In this study, we found that overexpression of YY1 suppressed proliferation and decreased the expression of long non-coding RNA (lncRNA) SOX2OT and its potential target gene SOX2 in PDAC cells. Luciferase reporter, electrophoretic mobility shift (EMSA), and chromatin immunoprecipitation (ChIP) assays revealed binding of YY1 to the SOX2OT promoter. Moreover, YY1 suppressed PDAC cell proliferation through SOX2OT transcriptional inhibition and subsequent decreased SOX2 expression. In addition, YY1 expression was statistically negatively correlated with SOX2OT and SOX2 expression in PDAC tissues and lower level expression of SOX2OT predicted better outcome in PDAC patients. These results confirmed the anti-proliferation effect of YY1 on PDAC cells, which was associated with SOX2 down-regulation in a SOX2OT-dependent mechanism. Although other undiscovered mechanisms may be involved in the YY1-mediated tumor suppression role, the present study suggests that SOX2OT may act as a tumor promotor in PDAC and may represent a valuable diagnostic and therapeutic target.

Association between LMP2/LMP7 genetic variability and cancer susceptibility, especially among Asians: evidence from a meta-analysis.

Low molecular mass protein (LMP) gene performs a critical role in the foreign antigen processing machine via the major histocompatibility complex-I (MHC-I) complex CD8+ cytotoxic T lymphocytes (CTL) pathway. Recent studies have reported the association of LMP2-60 G>A (rs17587) and LMP7-145 C>A (rs2071543) polymorphisms with various types of cancers, but the outcomes remained inconsistent. To obtain a reliable conclusion, we summarized available data and conducted a meta-analysis involving a total of 19 published studies. Evidences were obtained from the PubMed, Google Scholar, Web of Science and Chinese National Knowledge Infrastructure (CNKI) databases. The results demonstrated that the rs17587 and rs2071543 polymorphisms were associated with an increased cancer risk in the recessive and homozygote models. Stratified analyses by ethnicity indicated a significant association only in Asian population. Furthermore, rs17587 showed a greater susceptibility to gynecological cancers, while rs2071543 increased the risk of gastrointestinal and gynecological cancers. Our results indicate that the LMP2 rs17587 and LMP7 rs2071543 polymorphisms may act as risk factors for cancer, especially for Asian populations. Additional larger-scale multicenter studies should be performed to validate our results.

Visualizing myocardial inflammation in a rat model of type 4 cardiorenal syndrome by dual-modality molecular imaging.

Type 4 cardiorenal syndrome (CRS) is a life-threatening world health problem in which chronic kidney disease leads to progressive cardiovascular disease. In type 4 CRS, cardiac inflammation is an excellent target for both detection and therapy; however, this progression was underestimated by previous studies due to the lack of effective detection methods. To noninvasively visualize cardiac inflammation and monitor therapeutic efficacy of anti-inflammatory treatment in type 4 CRS, we here synthesized a dual-modality magneto-fluorescent nanoparticle (MNP) by combining ultrasmall superparamagnetic iron oxide nanoparticle and Rhodamine B for both magnetic resonance imaging (MRI) and optical imaging. This dual-functional MNP exhibited excellent performance such as high r2 relaxivity coefficient (283.4 mM(-1) s(-1)), high magnetism (96.7 emu/g iron) and a near neutral surface charge to minimize the reticuloendothelial system uptake. In vivo cardiac MRI showed significant negative contrast in the type 4 CRS rats, and the signal intensity on optical imaging was significantly higher in the type 4 CRS group compared with sham-operated and drug-treated groups. The specific targeting profile of MNPs to monocyte-macrophages was proven by histopathological analysis. Taken together, we demonstrate that this dual-modality strategy is feasible for noninvasively assessing myocardial inflammation and monitoring therapeutic efficacy in type 4 CRS.

Magnetic resonance imaging of post-ischemic blood-brain barrier damage with PEGylated iron oxide nanoparticles.

Blood-brain barrier (BBB) damage during ischemia may induce devastating consequences like cerebral edema and hemorrhagic transformation. This study presents a novel strategy for dynamically imaging of BBB damage with PEGylated supermagnetic iron oxide nanoparticles (SPIONs) as contrast agents. The employment of SPIONs as contrast agents made it possible to dynamically image the BBB permeability alterations and ischemic lesions simultaneously with T2-weighted MRI, and the monitoring could last up to 24 h with a single administration of PEGylated SPIONs in vivo. The ability of the PEGylated SPIONs to highlight BBB damage by MRI was demonstrated by the colocalization of PEGylated SPIONs with Gd-DTPA after intravenous injection of SPION-PEG/Gd-DTPA into a mouse. The immunohistochemical staining also confirmed the leakage of SPION-PEG from cerebral vessels into parenchyma. This study provides a novel and convenient route for imaging BBB alteration in the experimental ischemic stroke model.

[Study on the sorption behavior of tetracycline onto activated sludge].

The batch sorption methods were employed to investigate the sorption behavior of tetracycline (TC) on the activated sludge. It was shown that the mixed liquor suspended solids (MLSS) and the initial concentration of TC had great impacts on equilibrium time, adsorption capacity and adsorption rate. Compared with pseudo first-order model, pseudo second-order model showed the better agreement. At 10, 25 degrees C, the Langmuir model was the best isotherm to describe the experimental data for adsorption of TC on activated sludge, and the maximum adsorption capacities were 31.14, 70.95 mg x g(-1) respectively; at 40 degrees C, the linear isotherm confirmed the agreement. The data were also modeled by D-R isotherm to determine the type of adsorption. At 10 degrees C (E was 9.13 kJ x mol(-1)), the dominant type was physical, and at 40 degrees C (E was 7.07 kJ x mol(-1)), the dominant type was chemical. With the temperature increasing, the adsorption capacity increased. Ion exchange is one mechanism for adsorption of TC on activated sludge. When the initial concentrations of TC were 5, 10, 20 mg x L(-1), with the Na+ concentration increasing from 0 mol x L(-1) to 0.1 mol x L(-1), the adsorption capacities decreased by 15.32%, 15.00%, 20.12% respectively. The maximum adsorption capacity was got at pH 6 when pH varied from 5 to 10.