Antroquinonol Exerts Immunosuppressive Effect on CD8 +

Antroquinonol was investigated as antioxidant and inhibition of inflammatory responses. Our study was to evaluate its immunosuppressive effect on CD8+ T cells and protective effect on depigmentation. CD8+ T cells were treated with antroquinonol in vitro, and C57BL/6 mice were treated with antroquinonol with or without H2O2 in vivo for 50 consecutive days. We found antroquinonol could inhibit proliferation of CD8+ T cells and suppress the production of cytokines IL-2 and IFN-γ and T cell activation markers CD69 and CD137 in vitro. H2O2 treatment induced depigmentation and reduced hair follicle length, skin thickness, and tyrosinase expression in vivo. Whereas, antroquinonol obviously ameliorated depigmentation of mice skin and resisted the reduction of hair follicle length, skin thickness, and tyrosinase expression induced by H2O2. Antroquinonol decreased CD8+ T cell infiltration in mice skin, inhibited the production of IL-2 and IFN-γ, and decreased the expression of CXCL10 and CXCR3. Summarily, our data shows antroquinonol inhibits CD8+ T cell proliferation in vitro. It also reduces CD8+ T cell infiltration and proinflammatory cytokine secretion and suppresses the thinning of epidermal layer in vivo. Our findings suggest that antroquinonol exerts immunosuppressive effects on CD8+ T cell proliferation and activation to resist depigmentation induced by H2O2

Modified Dachengqi Tang improves decreased gastrointestinal motility in postoperative esophageal cancer patients

AbstractObjectiveTo investigate the clinical effects of modified Dachengqi Tang (DCQT) on promoting gastrointestinal motility in post-operative esophageal cancer patients.MethodsSixty postoperative esophageal cancer patients were enrolled and randomly assigned to the modified treatment group or the control group (30 patients in each group). Patients in the treatment group were given DCQT made from decocted herbs and administered via nasojejunal tube at a dosage of 150 mL. Gastrointestinal motility was assessed by recording time for recovery of bowel sounds, flatus, defecation, and the total amount of gastric drainage during the first three postoperative days. Plasma motilin (MTL) and vasoactive intestinal peptide (VIP) were measured one hour before and three days after surgery.ResultsCompared with the control group, the times to first bowel sound, flatus, and defecation were significantly shorter and there was less gastric drainage in the treatment group (P < 0.01, P < 0.01, P < 0.01, and P < 0.05, respectively). In the treatment group, postoperative plasma MTL was significantly higher (P < 0.01) and VIP was significantly lower than those in the control group (P < 0.05). There was no difference found in either MTL or VIP from before to after operation in the treatment group (P > 0.05). MTL was significantly lower and VIP was higher postoperatively in the control group, compared to before surgery (P < 0.01).ConclusionsModified DCQT effectively improved decreased gastrointestinal motility in postoperative esophageal cancer patients by increasing MTL and reducing VIP

Proteasome activator 28A: A clinical biomarker and pharmaceutical target in acute cerebral infarction therapy

Purpose: To determine the dynamic changes in serum levels of PA28α in patients with acute cerebral infarction (ACI), and to investigate its correlation with infarct size and neurological deficit of the disease. Methods: A total of 100 ACI patients and 100 healthy volunteers were recruited from The First Affiliated Hospital of Xinxiang Medical University as case and control groups, respectively. Their serum levels of PA28α were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The potential of PA28α in predicting the incidence of ACI was assessed by plotting ROC curves. Multivariate logistic regression analysis was conducted to investigate the risk factors of ACI. In addition, an ACI model in rats was established, and ACI rats were classified into 1, 3, 5, 7 and 14 day subgroups based on the duration post-ACI. Rats in the sham group served as control. Results: Serum level of PA28α was significantly higher in ACI patients than in controls. Moreover, the serum level of PA28α at admission was positively correlated to the NIHSS score and infarct volume of ACI patients. The level of PA28α in ACI rats gradually increased post-ACI, reaching a peak on day 7. The number of apoptotic brain cells in ACI rats gradually decreased after ACI. In addition, PA28α level was negatively correlated to the number of apoptotic brain cells in ACI rats (R2 = 0.5148, p &lt; 0.001). Conclusion: The serum level of PA28α is elevated in ACI patients, and is positively correlated to infarct volume and neurological deficit of the disease. The dynamic change in brain cell apoptosis post-ACI is negatively correlated to the serum level of PA28α. These findings may provide theoretical basis for the diagnosis and treatment of ACI

Neurospheres from rat adipose-derived stem cells could be induced into functional Schwann cell-like cells in vitro

<p>Abstract</p> <p>Background</p> <p>Schwann cells (SC) which are myelin-forming cells in peripheral nervous system are very useful for the treatment of diseases of peripheral nervous system and central nervous system. However, it is difficult to obtain sufficient large number of SC for clinical use, so alternative cell systems are desired.</p> <p>Results</p> <p>Using a procedure similar to the one used for propagation of neural stem cells, we could induce rat adipose-derived stem cells (ADSC) into floating neurospheres. In addition to being able to differentiate into neuronal- and glial-like cells, neurospheres could be induced to differentiate into SC-like cells. SC-like cells were bi- or tri-polar in shape and immunopositive for nestin and SC markers p75, GFAP and S-100, identical to genuine SC. We also found that SC-like cells could induce the differentiation of SH-SY5Y neuroblastoma cells efficiently, perhaps through secretion of soluble substances. We showed further that SC-like cells could form myelin structures with PC12 cell neurites in vitro.</p> <p>Conclusion</p> <p>These findings indicated that ADSC could differentiate into SC-like cells in terms of morphology, phenotype and functional capacities. SC-like cells induced from ADSC may be useful for the treatment of neurological diseases.</p

Effects of transition elements on the site preference, elastic properties and phase stability of L1 2 γ′-Co 3 (Al, W) from first-principles calculations

Abstract(#br)We performed a systematic study of alloying effects on the site preference, elastic properties and phase stability of L1 2 γ′-Co 3 (Al, W) in terms of the first-principles calculations. Up to twenty-one transition metal elements (Sc, Ti, V, Cr, Mn, Fe, Ni, Y, Zr, Nb, Mo, Tc, Ru. Rh, Pd, Hf, Ta, Re, Os, Ir and Pt) were considered in this work. We find that Sc, Ti, V, Cr, Mn, Y, Zr, Nb, Mo, Tc, Hf, Ta, Re and Os favor to occupy the Al site, and Fe, Ni, Ru. Rh, Pd, Ir and Pt favor to occupy the Co site, except for Y, Fe and Ru, other transition metal elements can stabilize the L1 2 γ′-Co 3 (Al, W) at 0 K. By using stress-strain method, the elastic properties including bulk modulus, shear modulus and Young’s modulus were evaluated. It is verified that the elastic properties of L1 2 γ′-Co 3 (Al, W) depend on not only volume change but also electron density as well as electronic configurations. The thermodynamic results of phase stability of L1 2 γ′-Co 3 (Al, W) reveal that Hf, Ti and Ta are the promising alloying elements to improve the stability of L1 2 γ′-Co 3 (Al, W)

Silver Nanoparticles Induce Tight Junction Disruption and Astrocyte Neurotoxicity in a Rat Blood-Brain Barrier Primary Triple Coculture Model

BACKGROUND: Silver nanoparticles (Ag-NPs) can enter the brain and induce neurotoxicity. However, the toxicity of Ag-NPs on the blood-brain barrier (BBB) and the underlying mechanism(s) of action on the BBB and the brain are not well understood. METHOD: To investigate Ag-NP suspension (Ag-NPS)-induced toxicity, a triple coculture BBB model of rat brain microvascular endothelial cells, pericytes, and astrocytes was established. The BBB permeability and tight junction protein expression in response to Ag-NPS, NP-released Ag ions, and polystyrene-NP exposure were investigated. Ultrastructural changes of the microvascular endothelial cells, pericytes, and astrocytes were observed using transmission electron microscopy (TEM). Global gene expression of astrocytes was measured using a DNA microarray. RESULTS: A triple coculture BBB model of primary rat brain microvascular endothelial cells, pericytes, and astrocytes was established, with the transendothelial electrical resistance values \u3e200 Ω·cm2. After Ag-NPS exposure for 24 hours, the BBB permeability was significantly increased and expression of the tight junction (TJ) protein ZO-1 was decreased. Discontinuous TJs were also observed between microvascular endothelial cells. After Ag-NPS exposure, severe mitochondrial shrinkage, vacuolations, endoplasmic reticulum expansion, and Ag-NPs were observed in astrocytes by TEM. Global gene expression analysis showed that three genes were upregulated and 20 genes were downregulated in astrocytes treated with Ag-NPS. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the 23 genes were associated with metabolic processes, biosynthetic processes, response to stimuli, cell death, the MAPK pathway, and so on. No GO term and KEGG pathways were changed in the released-ion or polystyrene-NP groups. Ag-NPS inhibited the antioxidant defense of the astrocytes by increasing thioredoxin interacting protein, which inhibits the Trx system, and decreasing Nr4a1 and Dusp1. Meanwhile, Ag-NPS induced inflammation and apoptosis through modulation of the MAPK pathway or B-cell lymphoma-2 expression or mTOR activity in astrocytes. CONCLUSION: These results draw our attention to the importance of Ag-NP-induced toxicity on the neurovascular unit and provide a better understanding of its toxicological mechanisms on astrocytes