Difference and its clinical significance of peripheral blood lymphocyte subsets between elderly and non-elderly patients with rheumatoid arthritis / 中华老年医学杂志

Objective:To investigate the difference of lymphocyte subsets between elderly patients with rheumatoid arthritis and non-elderly patients and its clinical significance.Methods:A total of 124 patients with rheumatoid arthritis in Affiliated Hospital of Nantong University from January, 2017 to December, 2019 were enrolled.The patients were divided into elderly group(≥60 years old, 34 cases)and non-elderly group(<60 years old, 90 cases). Rheumatoid arthritis activity(DAS-28)scoring was performed for each patient.Peripheral blood mononuclear cells(PBMCs)were extracted by Ficoll density centrifugation.Lymphocytes were labeled and detected by 18-color flowcytometry with more than 30 fluorescent antibodies.Results:DAS-28 scoring showed that the disease activity score of the elderly group(4.56±1.89)was higher than that of the non-elderly group(3.37±1.49)( t=3.633, P<0.001). Flow cytometry showed that MAIL%T(mucus-associated lymphoid tissue T cell subset)( Z=-2.798, P=0.005), Tn%CD8 T cells(initial CD8 T cells)( Z=-2.179, P=0.029), VD2% T(Vδ2+ T, γδT cell subtype)( Z=-2.806, P=0.005), PD1-CD28-%Th( Z=-2.050, P=0.040)and IGM+ D-%B( Z=-2.376, P=0.017)were lower in the elderly group than in the non-elderly group.While, CD45+ CD27+ %CD8 T cells( Z=-3.069, P=0.002), abT%T cell(αβT cells)( Z=-2.103, P=0.035), CD27-CD28+ %T cells( Z=-2.341, P=0.019), ASC%PBMC( Z=-2.341, P=0.019)and ASC%CD19+ ( Z=-2.000, P=0.046)subgroup expression were higher in the elderly group than in the non-elderly group. Conclusions:The disease activity of elderly patients with rheumatoid arthritis is significantly higher than that of younger patients.The expressions of abT%T and CD4% abT in effector T cells of elderly patients with rheumatoid arthritis are higher than those of younger patients, while the expression of VD2% T is lower.The expression level of CD45RA+ CD27+ %CD8 T with cytotoxic effect is higher; However, the expression level of Tn%CD8 T in naive cells is lower.

Mycn regulates intestinal development through ribosomal biogenesis in a zebrafish model of Feingold syndrome 1.

Feingold syndrome type 1, caused by loss-of-function of MYCN, is characterized by varied phenotypes including esophageal and duodenal atresia. However, no adequate model exists for studying the syndrome's pathological or molecular mechanisms, nor is there a treatment strategy. Here, we developed a zebrafish Feingold syndrome type 1 model with nonfunctional mycn, which had severe intestinal atresia. Single-cell RNA-seq identified a subcluster of intestinal cells that were highly sensitive to Mycn, and impaired cell proliferation decreased the overall number of intestinal cells in the mycn mutant fish. Bulk RNA-seq and metabolomic analysis showed that expression of ribosomal genes was down-regulated and that amino acid metabolism was abnormal. Northern blot and ribosomal profiling analysis showed abnormal rRNA processing and decreases in free 40S, 60S, and 80S ribosome particles, which led to impaired translation in the mutant. Besides, both Ribo-seq and western blot analysis showed that mTOR pathway was impaired in mycn mutant, and blocking mTOR pathway by rapamycin treatment can mimic the intestinal defect, and both L-leucine and Rheb, which can elevate translation via activating TOR pathway, could rescue the intestinal phenotype of mycn mutant. In summary, by this zebrafish Feingold syndrome type 1 model, we found that disturbance of ribosomal biogenesis and blockage of protein synthesis during development are primary causes of the intestinal defect in Feingold syndrome type 1. Importantly, our work suggests that leucine supplementation may be a feasible and easy treatment option for this disease.

More than just statics: altered complexity of dynamic amplitude of low-frequency fluctuations in the resting brain after stroke.

Objective.Previous neuroimaging studies mainly focused on static characteristics of brain activity, and little is known about its characteristics over time, especially in post-stroke (PS) patients. In this study, we aimed to investigate the static and dynamic characteristics of brain activity after stroke using functional magnetic resonance imaging (fMRI).Approach.Twenty ischemic PS patients and nineteen healthy controls (HCs) were recruited to receive a resting-state fMRI scanning. The static amplitude of low-frequency fluctuations (sALFFs) and fuzzy entropy of dynamic ALFF (FE-dALFF) were applied to identify the stroke-induced alterations.Main results.Compared with the HCs, PS patients showed significantly increased FE-dALFF values in the right angular gyrus (ANG), bilateral precuneus (PCUN), and right inferior parietal lobule (IPL) as well as significantly decreased FE-dALFF values in the right postcentral gyrus (PoCG), right dorsolateral superior frontal gyrus (SFGdor), and right precentral gyrus (PreCG). The receiver operating characteristic analyses demonstrated that FE-dALFF and sALFF possess comparable sensitivity in distinguishing PS patients from the HCs. Moreover, a significantly positive correlation was observed between the FE-dALFF values and the Fugl-Meyer Assessment (FMA) scores in the right SFGdor (r= 0.547), right IPL (r= 0.522), and right PCUN (r= 0.486).Significance.This study provided insight into the stroke-induced alterations in static and dynamic characteristics of local brain activity, highlighting the potential of FE-dALFF in understanding neurophysiological mechanisms and evaluating pathological changes.

The effectiveness of cupping therapy on chronic fatigue syndrome: A single-blind randomized controlled trial.

BACKGROUND: and purpose: We investigated the effectiveness of cupping therapy with three different pressures in patients with chronic fatigue syndrome (CFS). MATERIALS AND METHODS: The participants were randomly assigned to three groups, as follows: cupping pressure of -0.02 mpa (n = 38), -0.03 mpa (n = 38), or -0.05 mpa (n = 36). Each group received cupping treatment that consisted of 10 sessions over 5 weeks (2 sessions per week). The primary outcomes were Fatigue Scale (FS-14) score and Fatigue Assessment Instrument (FAI) score after 5 and 10 sessions. The secondary outcomes were the Self-Rating Anxiety Scale (SAS) score, the Self-Rating Depression Scale (SDS) score, and the Pittsburgh Sleep Quality Index (PSQI) score. RESULTS: There were 91 participants who completed the trial. After five sessions of treatment, the primary outcome of FS-14 score decreased by 3.20 (2.19, 4.21) in the -0.02 mpa group, by 2.39 (1.51, 3.27) in the -0.03 mpa group, and by 3.40 (2.28, 4.52) in the -0.05 mpa group (P = 0.667). After 10 sessions of treatment, the outcome of FS-14 score decreased by 5.00 (3.79, 6.21) in the -0.02 mpa group, by 4.06 (3.07, 5.05) in the -0.03 mpa group, and by 4.77 (3.52, 5.94) in the -0.05 mpa group (P = 0.929). And, the results were statistically different between 5 sessions and 10 sessions of treatment (P < 0.01). However, there were no statistical differences in FAI, SAS, SDS, and PSQI scores between the three groups after 5 sessions and 10 sessions of treatment. CONCLUSIONS: In conclusion, cupping therapy has significantly relieved fatigue symptoms and improved emotion and sleep condition of CFS patients, and 10 sessions of treatment had superior results compared with 5 sessions in each group. Moreover, in 5 sessions of treatment, cupping with high pressure showed better improvement in fatigue syndromes and sleep condition according to effective rates. TRIAL REGISTRATION: Chinese clinical trial registry (ChiCTR1800017590); Ethical approval number: ChiECRCT-20180085.

Dewatering efficiency of sewage sludge during Fe2+-activated persulfate oxidation: Effect of hydrophobic/hydrophilic properties of sludge EPS.

To clarify the effect of the hydrophobic/hydrophilic polarity of extracellular polymeric substances (EPS) on sludge filterability improvement during S2O82-/Fe2+ oxidation, waste activated sludge (WAS), glucose-fed hydrophilic sludge (HPI-WAS), and sodium acetate-fed hydrophobic sludge (HPO-WAS) samples were cultivated, and their dewatering behaviors were individually explored. Experimental results showed that S2O82- oxidation effectively disintegrated the polymeric EPS and led to a more significant reduction in the water content for HPO-WAS than for HPI-WAS (12.87-15.23% vs 9.31-12.12%), especially regarding the bound water (Wb) content. After oxidation, as high as 38.88-42.61% of the Wb within HPO-WAS samples were declined, much higher than the HPI-WAS samples (19.27-29.20%). Specifically, carbohydrates within sludge EPS negatively influenced the dewatering process of S2O82-/Fe2+ oxidation. By contrast, abundant existence of humic acids and polymeric proteinaceous components (especially those hydrophilic proteins and transitional humic acids) within the sludge EPS exhibited a converse trend. FT-IR and EEM spectral, as well as particle sizes variation for the sludge samples before and after S2O82-/Fe2+ oxidation was also evaluated. This study provides new insight into the enhancement of S2O82-/Fe2+ oxidation for sludge dewatering based on polarity analysis of EPS.

Adsorption behaviors of Cu2+, Zn2+ and Cd2+ onto proteins, humic acid, and polysaccharides extracted from sludge EPS: Sorption properties and mechanisms.

To clarify the adsorption behaviors of typical heavy metals onto sludge extracellular polymeric substances (EPS), the adsorption capacities and mechanisms, as well as the contributions of the different EPS components (proteins, humic acids and polysaccharides), to the adsorption of Zn2+, Cu2+ and Cd2+ were separately explored. Overall, proteins exhibited a relatively high adsorption capacity for the three metals ions, followed by humic acid, whereas least for polysaccharides. The adsorption of Cu2+ and Cd2+ onto proteins, humic acid and polysaccharides fit well to the Freundlich isotherm, whereas Langmuir model was the best fit for Zn2+ bindings onto polysaccharides/humic acid. The binding of Cu2+, Zn2+ and Cd2+ onto the three EPS components was exothermically favorable, and significant electrostatic interactions were observed for the heavy metals sorption onto humic acid and proteins. In addition, the effect of metal ions sorption on the spectrum of the proteins, polysaccharides and humic acid was also explored.

Optimization of the co-digestion of sewage sludge, maize straw and cow manure: microbial responses and effect of fractional organic characteristics.

The aim of this study was to evaluate the efficiency and optimization of co-digestion using sewage sludge (SS), maize straw (MS) and cow manure (CM) as feeds, and the effects of the mixing ratio and C/N ratio of the substrates were analyzed in detail. Among the three substrates tested, CM/MS exhibited better digestion than CM/SS and SS/MS in terms of all measures, including total daily biogas and net methane volume production, due to the hydrophilic characteristics and high level of biodegradability of CM, as well as its higher C/N ratio. The average biogas production was 613.8 mL/g VS for the co-digestion of CM/MS at a feed concentration of 15 g VS/L and using a 1:1 mixing ratio (C/N ratio of 28.3). The co-digestion of SS/CM/MS performed better than the individual digestion of the components because of the balanced C/N ratios and supply of carbon. The optimum conditions for maximizing methane potential were an SS:CM:MS ratio of 30:35:35 and a bulk VS concentration of 15.0 g VS/L, which led to a maximum methane production of 8047.31 mL (C/N ratio of 12.7). The high-throughput sequencing analysis showed clear differences in microbial communities during the entire co-digestion process.

Adsorption mechanism of ZnO and CuO nanoparticles on two typical sludge EPS: Effect of nanoparticle diameter and fractional EPS polarity on binding.

Worldwide application of nanotechnology has led to an increasingly release of nanoparticles in wastewater treatment systems, and thus into sewage sludge, which potentially impairs the disposal of sewage sludge. Here, the binding process, adsorption characteristics, and the contribution of fractional polarity of extracellular polymeric substances (EPS) of anaerobic granular sludge (AGS) and activated sludge (AS) to the nano-ZnO and nano-CuO adsorption were investigated. Briefly, CuO-NPs can be more efficiently adsorbed by the EPS-AGS than that of ZnO-NPs (1.31 ±â€¯0.08 g/g VS vs 0.53 ±â€¯0.04 g/g VS), and a smaller diameter of nanoparticles benefited the adsorption processes. Hydrophobic EPS (HPO-A and HPO-N) within these two sludge were more effective in removing nano-CuO and ZnO than were the hydrophilic fraction. For example, HPO-A and HPO-N obtained from AGS showed a relatively higher adsorption abilities (in g/g VS) of 2.09 ±â€¯0.12 and 2.27 ±â€¯0.14, respectively, for nano-CuO, much higher than HPI (0.76 ±â€¯0.04 g/g VS). Structural variations of the EPS before and after nanoparticles sorption were evaluated via the analysis of infrared spectroscopy, which showed that the functional structures of hydroxyl, amino, carboxyl, amide groups and C-O-C groups played a major role in nanoparticles binding/removal. Sorption process of nano-CuO and nano-ZnO on unfractionated EPS well fitted by Langmuir isotherm, as well as a pseudo second-order kinetic model. However, adsorption process of HPO-A can be better simulated by Freundlich equation.

Application of pharmacogenomics in individualized administration of cytotoxic antitumor drugs / 医学研究生学报

Cytotoxic anti-tumor drugs are characterized by narrow therapeutic indexes, severe toxicity and great difference in the effects of individualized therapies, while studies of pharmacogenomics (PGx) can provide biomarkers for predicting the efficacy and toxicity of chemotherapy drugs. PGx biomarkers play an important role in predicting the safety, toxicity and effects of drugs in the treatment of tumors. By identifying specific polymorphisms of PGx biomarkers, physicians could select and customize medication regimens based on the patient's genetic profile. This review focuses on the germline PGx biomarkers that are currently used for guiding therapeutic decisions and have potential clinical application values, including thiopurine S-methyltransferase and thiopurine, NUDT15 and thiopurine, UGT1A1 and irinotecan, DPYD and fluorouracil, CYP2D6 and tamoxifen, and TPMP and cisplatin.

Research progress on Chinese materia medica pairs and their active components against cerebral ischemia / 中草药

The in-depth study on the law of drug pair compatibility and its mechanism has important scientific connotation for the clinical prescriptions and the improvement of curative effect. In recent years, many prevention and treatment of cerebral ischemic injury found that the rational use of Chinese materia medica pairs by optimizing the combination of Chinese medicine compound played a multi-target, multi-level role in the ischemic brain tissue of the neurovascular units, multi-channel regulation of the relevant signal pathways, which can significantly reduce the damage of ischemic penumbra brain tissue, relieve the inflammatory cascade and reperfusion injury caused by cerebral ischemia injury, promptly restore the blood flow in the brain and effectively protect the neurons, achieve “re-flow” and “brain protect” similar effects, and further promote the repair of nerve function.

Cholesterol modulates function of connexin 43 gap junction channel via PKC pathway in H9c2 cells.

It has been shown that cholesterol modulates activity of protein kinase C (PKC), and PKC phosphorylates connexin 43 (Cx43) to regulate its function, respectively. However, it is not known whether cholesterol modulates function of Cx43 through regulating activity of PKC. In the present study, we demonstrated that cholesterol enrichment reduced the dye transfer ability of Cx43 in cultured H9c2 cells. Western blot analysis indicated that cholesterol enrichment enhanced the phosphorylated state of Cx43. Immunofluorescent images showed that cholesterol enrichment made the Cx43 distribution from condensed to diffused manner in the interface between the cells. In cholesterol enriched cells, PKC antagonists partially restored the dye transfer ability among the cells, downregulated the phosphorylation of Cx43 and redistributed Cx43 from the diffused manner to the condensed manner in the cell interface. In addition, reduction of cholesterol level suppressed PKC activity to phosphorylate Cx43 and restored Cx43 function in PKC agonist-treated cells. Furthermore, we demonstrated that cholesterol enrichment upregulated the phosphorylated state of Cx43 at Ser368, while PKC antagonists reversed the effect. Taken together, cholesterol level in the cells plays important roles in regulating Cx43 function through activation of the PKC signaling pathway.

Chlorpromazine confers neuroprotection against brain ischemia by activating BKCa channel.

Chlorpromazine (CPZ) is a well-known antipsychotic drug, still widely being used to treat symptoms of schizophrenia, psychotic depression and organic psychoses. We have previously reported that CPZ activates the BKCa (KCa1.1) channel at whole cell level. In the present study, we demonstrated that CPZ increased the single channel open probability of the BKCa channels without changing its single channel amplitude. As BKCa channel is one of the molecular targets of brain ischemia, we explored a possible new use of this old drug on ischemic brain injury. In middle cerebral artery occlusion (MCAO) focal cerebral ischemia, a single intraperitoneal injection of CPZ at several dosages (5mg/kg, 10mg/kg and 20mg/kg) could exert a significant neuroprotective effect on the brain damage in a dose- and time-dependent manner. Furthermore, blockade of BKCa channels abolished the neuroprotective effect of CPZ on MCAO, suggesting that the effect of CPZ is mediated by activation of the BKCa channel. These results demonstrate that CPZ could reduce focal cerebral ischemic damage through activating BKCa channels and merits exploration as a potential therapeutic agent for treating ischemic stroke.

Auditory sexual difference in the large odorous frog Odorrana graminea.

Acoustic communication is an important behavior in frog courtship. Male and female frogs of most species, except the concave-eared torrent frog Odorrana tormota, have largely similar audiograms. The large odorous frogs (Odorrana graminea) are sympatric with O. tormota, but have no ear canals. The difference in hearing between two sexes of the frog is unknown. We recorded auditory evoked near-field potentials and single-unit responses from the auditory midbrain (the torus semicircularis) to determine auditory frequency sensitivity and threshold. The results show that males have the upper frequency limit at 24 kHz and females have the upper limit at 16 kHz. The more sensitive frequency range is 3-15 kHz for males and 1-8 kHz for females. Males have the minimum threshold at 11 kHz (58 dB SPL), higher about 5 dB than that at 3 kHz for females. The best excitatory frequencies of single units are mostly between 3 and 5 kHz in females and at 7-8 kHz in males. The underlying mechanism of auditory sexual differences is discussed.

Nicotine exerts neuroprotective effects against ß-amyloid-induced neurotoxicity in SH-SY5Y cells through the Erk1/2-p38-JNK-dependent signaling pathway.

Epidemiological data have indicated that smoking tobacco can decrease the risk of developing Alzheimer's disease (AD). Nicotine, a main component of tobacco, has been shown to have therapeutic effects in AD. The aim of the present study was to assess the neuroprotective effects of nicotine against toxicity induced by ß-amyloid (Aß) in relation to cell apoptosis, and to elucidate the role of the activation of the Erk1/2-p38-JNK pathway and the modulation of anti-apoptotic proteins in the nicotine-induced neuroprotective effects. We performed in vitro and in vivo experiments using SH-SY5Y cells and C57BL/6 mice, respectively. The effects of nicotine on cell apoptosis were determined by flow cytmetry and microscopic observation. The effects of nicotine on the expression of anti-apoptotic proteins were also determined by western blot analysis. Our results demonstrated that nicotine protected the SH-SY5Y cells against Aß25-35-induced toxicity by inhibiting apoptosis and upregulating the expression of anti-apoptotic proteins. As shown by our in vivo experiments, nicotine effectively ameliorated the impairment in spatial working memory induced by Aß25-35; this was confirmed by a Morris water maze navigation test and further supported by the upregulation of Bcl-2 in the hippocampus of Aß25-35-injected mice treated with nicotine. The phosphorylation of Erk1/2, p38 and JNK increased following treatment with nicotine in the SH-SY5Y cells, whereas caspase-3 activation was inhibited by treatment with nicotine prior to exposure to Aß25-35. Of note, these effects of nicotine against Aß25-35-induced damage were abolished by inhibitors of Erk1/2, p38 and JNK phosphorylation. These findings suggest that nicotine prevents Aß25-35-induced neurotoxicity through the inhibition of neuronal apoptosis, and may thus prove to be a potential preventive or therapeutic agent for AD.

Expression of yeast acyl-delta9 desaturase for fatty acid biosynthesis in tobacco / 生物工程学报

Palmitoleic acid (16:1delta9), an unusual monounsaturated fatty acid, is highly valued for human nutrition, medication and industry. Plant oils containing large amounts of palmitoleic acid are the ideal resource for biodiesel production. To increase accumulation of palmitoleic acid in plant tissues, we used a yeast (Saccharomyees cerevisiae) acyl-CoA-delta9 desaturase (Scdelta9D) for cytosol- and plastid-targeting expression in tobacco (Nicotiana tabacum L.). By doing this, we also studied the effects of the subcellular-targeted expression of this enzyme on lipid synthesis and metabolism in plant system. Compared to the wild type and vector control plants, the contents of monounsaturated palmitoleic (16:1delta9) and cis-vaccenic (18:1delta11) were significantly enhanced in the Scdelta9D-transgenic leaves whereas the levels of saturated palmitic acid (16:0) and polyunsaturated linoleic (18:2) and linolenic (18:3) acids were reduced in the transgenics. Notably, the contents of 16:1delta9 and 18:1delta11 in the Scdelta9D plastidal-expressed leaves were 2.7 and 1.9 folds of that in the cytosolic-expressed tissues. Statistical analysis appeared a negative correlation coefficient between 16:0 and 16:1delta9 levels. Our data indicate that yeast cytosolic acyl-CoA-delta9 desaturase can convert palmitic (16:0) into palmitoleic acid (16:1delta9) in high plant cells. Moreover, this effect of the enzyme is stronger with the plastid-targeted expression than the cytosol-target expression. The present study developed a new strategy for high accumulation of omega-7 fatty acids (16:1delta9 andl8:1delta11) in plant tissues by protein engineering of acyl-CoA-delta9 desaturase. The findings would particularly benefit the metabolic assembly of the lipid biosynthesis pathway in the large-biomass vegetative organs such as tobacco leaves for the production of high-quality biodiesel.

[Expression of A-kinase anchor protein 95, cyclin E2, and connexin 43 in lung cancer tissue, clinical significance of their expression, and their expression correlation].

OBJECTIVE: To study the expression of A-kinase anchor protein 95 (AKAP95), cyclin E(2), and connexin 43 (Cx43) in lung cancer tissue, the clinical significance of their expression, and the expression correlation among the three proteins. METHODS: Fifty-one samples of lung cancer tissue were examined by immunohistochemistry to measure the expression of AKAP95, cyclin E2, and Cx43. RESULTS: The positive rate of AKAP95 expression in lung cancer tissue was significantly higher than that in paracancerous tissue (82.35% vs 33.33%, P < 0.05); AKAP95 expression was associated with the cell differentiation and histopathological type of lung cancer (P < 0.05). The positive rate of cyclin E(2) expression in lung cancer tissue was significantly higher than that in paracancerous tissue (43.14% vs 13.33%, P < 0.05); cyclin E(2) expression was associated with the lymph node metastasis and histopathological type of lung cancer (P < 0.05). The positive rate of Cx43 expression in lung cancer tissue was lower than that in paracancerous tissue (60.78% vs 80.00%); Cx43 expression was associated with the cell differentiation, lymph node metastasis, and histopathological type of lung cancer (P < 0.05). There was correlation between each two of AKAP95 expression, cyclin E(2) expression, and Cx43 expression in lung cancer tissue. CONCLUSION: High expression of AKAP95 and cyclin E(2) plays an important role in the occurrence and development of lung cancer. AKAP95 expression is associated with the cell differentiation and histopathological type of lung cancer, and cyclin E2 expression is associated with lymph node metastasis and histopathological type. There is correlation between each two of AKAP95 expression, cyclin E(2) expression, and Cx43 expression in lung cancer tissue.

Nicotine stimulated bone marrow-derived dendritic cells could augment HBV specific CTL priming by activating PI3K-Akt pathway.

Our previous studies have revealed that nicotine-treated immature dendritic cells (imDCs) have anti-tumor effects in murine lymphoma models. The present study is to explore HBV-specific CTL priming and its cytolytic activities of nicotine-treated murine DCs, the mechanism of α7 nicotinic acetylcholine receptor (nAChR) up-regulation by nicotine and the efficiency of nicotine with other cytokines. To address these hypotheses, bone marrow-derived imDCs were stimulated by nicotine and expression of α7 nAChR was firstly determined by flow cytometry and Western blot. Then, DCs-dependent HBV-specific T cell proliferation and IL-12 secretion were secondly determined by BrdU cell proliferation assay and ELISA, respectively. The HBV-specific CTL priming and its activities were further explored by intraperitoneal transfer of nicotine treated imDCs. The mechanism of nicotine up-regulating α7 nAChR was finally explored by Western blot. The results showed that: first, the maximal activation of PI3K and Akt was reached at 30 and 60-120 min respectively after nicotine stimulation. Nicotine up-regulated the expression of α7 nAChR by activating PI3K-Akt pathway in murine DCs; secondly, nicotine stimulation could enhance DCs' ability of HBV-specific T cell proliferation and IL-12 secretion; thirdly, adoptive transfer of nicotine stimulated DCs could induce HBV specific CTL priming in vivo and those CTL had cytolytic activities; fourthly, nicotine had equal efficiencies to 2 ng/ml IFN-γ in DCs-mediated T cell proliferation. All these data presented here indicated that nicotine treated imDCs might be considered as a potential candidate for HBV immunotherapy.

The suppressive effects of Bursopentine (BP5) on oxidative stress and NF-ĸB activation in lipopolysaccharide-activated murine peritoneal macrophages.

BACKGROUND/AIM: Bursopentine (BP5) is a novel thiol-containing pentapeptide isolated from chicken bursa of Fabricius, and is reported to exert immunomodulatory effects on B and T lymphocytes. It has been found that some thiol compounds, such as glutathione (GSH) and N-acetylcysteine (NAC) protect living cells from oxidative stress. This led us to investigate whether BP5 had any ability to protect macrophages from oxidative stress as well as any mechanism that might underlie this process. METHODS: Murine peritoneal macrophages activated by lipopolysaccharide (LPS) (2 µg/ml) were treated with single bouts (0, 25, 50, and 100 µM) of BP5. RESULTS: BP5 potently suppressed the markers for oxidative stress, including nitric oxide (NO), reactive oxygen species (ROS), lipid peroxidation, and protein oxidation. It also decreased the expression and activity of inducible nitric oxide synthase (iNOS) and promoted a protective antioxidant state by elevating GSH content and by activating the expression and activity of certain key antioxidant and redox enzymes, including glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT). This suppressive effect on oxidative stress was accompanied by down-regulated expression and activity of nuclear factor kappa B (NF-κB). CONCLUSION: These findings demonstrate that BP5 can protect LPS-activated murine peritoneal macrophages from oxidative stress. BP5 may have applications as an anti-oxidative stress reagent.

Lipopolysaccharide and dose of nicotine determine the effects of nicotine on murine bone marrow-derived dendritic cells.

The reported effects of nicotine on dendritic cells (DCs) are controversial. To investigate the factors which determine the effects of nicotine on DCs, immature dendritic cells (imDCs) induced from murine bone marrow were treated with different doses of nicotine with or without lipopolysaccharides (LPS). The morphology and expression of the co-stimulatory molecules CD80, CD86, CD40 and CD54 were observed and determined by microscopy and flow cytometry, respectively. The results showed that, firstly, nicotine treatment promoted the development of DC precursors into imDCs with a semi-mature phenotype revealed by a higher expression of CD11c and more branched projections. Secondly, lower doses of nicotine (16.5 ng/ml), but not higher (200 µg/ml), up-regulated the expression of the co-stimulatory molecules CD80, CD40 and CD54 on imDCs. Co-administration of LPS and nicotine revealed differential effects on co-stimulatory molecule expression on imDCs. Thirdly and importantly, treatment with lower doses of nicotine (16.5 ng/ml) did not augment expression of the CD80, CD86, CD40 and CD54 molecules in mature DCs. Fourthly and interestingly, high doses of nicotine (more than 165 µg/ml) revealed pro-apoptotic activity but lower doses of nicotine (16.5-0.165 ng/ml) achieved an anti-apoptotic effect on imDCs. All data presented here indicate that the controversial effects of nicotine on DCs may be due to the LPS of the nicotinic environment and the dose of nicotine used.

Apply research of MRI combined with 1H-MRS in meningiomas / 国际肿瘤学杂志

Objective To evaluate the roles of magnetic resonance imaging and proton magnetic resonance spectroscopy(1H-MRS) in the diagnosis of meningiomas. Methods 98 patients with meningiomas underwent conventional pre-contrast MR and contrast MR. Among them, 28 cases had two dimensional single voxel or multi voxel 1 H-MRS simultaneously both in the lesion's region and the contralateral side. Results On precontrast MR images of 98 cases, T1 WI showed 58.1% (61/105) isointensities, 31.4% (33/105) faintly low intensities and 10. 5% (11/105) mixed intensities; T2WI showed 40. 0% (42/105) isointensities, 41.0%(43/105) hyperintensities, 10.5% (11/105) faintly low intensities and 8.5% (9/105) mixed intensities. After administration of Gd-DTPA, the solid part of the tumors exhibited various enhancement in all the 98 cases.28 cases of MRS exhibited specific different spectral peaks, including increased of choline-containing compounds(Cho), absent or decreased of acetylaspartate(NAA), and the unchanged of creatine(Cr). The value of NAA, Cr, Cho, NAA/Cr, Cho/Cr, NAA/Cho in the tumor center of meningioma were 0. 09 ± 0.06,0.31 ± 0. 22, 0.46 ± 0. 16, 0.33 ± 0. 42, 1.50 ± 0. 68, 0. 15 ± 0.08, compared with the contralateral normal region, Cr has no significant difference (P ＞ 0. 05), NAA, Cho, NAA/Cr, Cho/Cr, NAA/Cho had significantly differences(P ＜ 0.05). Conclusion Conventional pre-contrast MR and contrast MR is the most important dignostic means for meningiomas, 1H-MRS combined with MRI can improve the diagnostic accuracy of meningiomas.