Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro

Thymosin alpha 1 (Tα1) has been shown to have beneficial effects on numerous immune system parameters, but little is known about the effects of Tα1 on patients with gastric carcinoma. The objective of this study was to determine the effect of Tα1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro, and to evaluate its efficacy as an immunoregulatory factor in patients with gastric carcinoma. We compared the effect of Tα1 on the frequency of CD4+ and CD8+ T cells, especially the CD4+CD25+Foxp3+ Tregs in peripheral blood mononuclear cells (PBMCs) from gastric carcinoma patients (N = 35) and healthy donors (N = 22). We also analyzed the changes in the proliferation of PBMCs in response to treatment with Tα1, and examined the production of Th1, Th2, and Th17 cytokines by PBMCs and tumor-infiltrating lymphocytes. The treatment of PBMCs from gastric cancer patients, with Tα1 (50 µg/mL) alone increased the percentage of CD4+CD25+Foxp3+ (suppressive antitumor-specific Tregs) from 1.68 ± 0.697 to 2.19 ± 0.795% (P < 0.05). Our results indicate that Tα1 increases the percentage of Tregs and IL-1β, TNF-α, and IL-6 in vitro.

Overexpression of Fc receptor-like 1 associated with B-cell activation during hepatitis B virus infection

The role of B cells in the pathogenesis of hepatitis B virus (HBV) infection has not been explored in depth. In the present study, the activation status of B cells from peripheral blood of healthy controls (N = 20) and patients with acute hepatitis B (AHB, N = 15) or chronic hepatitis B (CHB, N = 30) was evaluated by measuring the expression levels of B-cell activation markers CD69 and CD86, using quantitative real-time PCR and flow cytometry. Moreover, the potential mechanism underlying B-cell activation during HBV infection was further investigated by analyzing the expression profile of FCRL1, an intrinsic activation molecule of B cells. An elevation in the levels of B-cell activation markers including CD69 and CD86 was observed in the AHB patients (44.31 ± 9.27, 27.64 ± 9.26%) compared to CHB patients (30.35 ± 11.27, 18.41 ± 6.56%, P < 0.05), which was still higher than healthy controls (12.23 ± 7.84, 8.22 ± 3.43%, P < 0.05). Furthermore, the expression of FCRL1 was found to be similar to B-cell activation markers, which was highest in AHB patients (70.15 ± 17.11%), lowest in healthy donors (36.32 ± 9.98%, P < 0.05) and half-way between these levels in patients with CHB (55.17 ± 12.03%, P < 0.05). The results were positively associated with aberrant B-cell activation. These data suggest that B cells can play a role in HBV infection, and therefore more effort should be devoted to exploring their functions.

Effect of hepatocyte growth factor and angiotensin II on rat cardiomyocyte hypertrophy

Angiotensin II (Ang II) plays an important role in cardiomyocyte hypertrophy. The combined effect of hepatocyte growth factor (HGF) and Ang II on cardiomyocytes is unknown. The present study was designed to determine the effect of HGF on cardiomyocyte hypertrophy and to explore the combined effect of HGF and Ang II on cardiomyocyte hypertrophy. Primary cardiomyocytes were isolated from neonatal rat hearts and cultured in vitro. Cells were treated with Ang II (1 µM) alone, HGF (10 ng/mL) alone, and Ang II (1 µM) plus HGF (10 ng/mL) for 24, 48, and 72 h. The amount of [³H]-leucine incorporation was then measured to evaluate protein synthesis. The mRNA levels of β-myosin heavy chain and atrial natriuretic factor were determined by real-time PCR to evaluate the presence of fetal phenotypes of gene expression. The cell size of cardiomyocytes was also studied. Ang II (1 µM) increased cardiomyocyte hypertrophy. Similar to Ang II, treatment with 1 µM HGF promoted cardiomyocyte hypertrophy. Moreover, the combination of 1 µM Ang II and 10 ng/mL HGF clearly induced a combined pro-hypertrophy effect on cardiomyocytes. The present study demonstrates for the first time a novel, combined effect of HGF and Ang II in promoting cardiomyocyte hypertrophy.

AKT inhibitor suppresses hyperthermia-induced Ndrg2 phosphorylation in gastric cancer cells

Hyperthermia is one of the most effective adjuvant treatments for various cancers with few side effects. However, the underlying molecular mechanisms still are not known. N-myc downstream-regulated gene 2 (NDRG2), a tumor suppressor, has been shown to be involved in diverse cellular stresses including hypoxia, lipotoxicity, etc. In addition, Ndrg2 has been reported to be related to progression of gastric cancer. In the current study, our data showed that the apoptosis rate of MKN28 cells increased relatively rapidly to 13.4% by 24 h after treatment with hyperthermia (42°C for 1 h) compared to 5.1% in control cells (P < 0.05). Nevertheless, there was no obvious change in the expression level of total Ndrg2 during this process. Further investigation demonstrated that the relative phosphorylation levels of Ndrg2 at Ser332, Thr348 increased up to 3.2- and 1.9-fold (hyperthermia groupvs control group) at 3 h in MKN28 cells, respectively (P < 0.05). We also found that heat treatment significantly increased AKT phosphorylation. AKT inhibitor VIII (10 µM) decreased the phosphorylation level of Ndrg2 induced by hyperthermia. Accordingly, the apoptosis rate rose significantly in MKN28 cells (16.4%) treated with a combination of AKT inhibitor VIII and hyperthermia compared to that (6.8%) of cells treated with hyperthermia alone (P < 0.05). Taken together, these data demonstrated that Ndrg2 phosphorylation could be induced by hyperthermia in an AKT-dependent manner in gastric cancer cells. Furthermore, AKT inhibitor VIII suppressed Ndrg2 phosphorylation and rendered gastric cancer cells susceptible to apoptosis induced by hyperthermia.

Correlation between interleukin-18promoter -607C/A polymorphism and susceptibility to ischemic stroke

Single nucleotide polymorphisms in the promoter region ofinterleukin-18 (IL-18), an inflammatory cytokine, have been linked to susceptibility to many diseases, including cancer and immune dysfunction. Here, we explored the potential association between theIL-18 -607C/A (rs1946518) promoter region polymorphism and susceptibility to ischemic stroke (IS). This locus was amplified from peripheral blood samples of 386 IS patients (cases) and 364 healthy individuals (controls) by the polymerase chain reaction with sequence-specific primers. Significant differences were observed by the χ2 test in the -607C/A (rs1946518) genotype and allele frequencies between cases and controls (P < 0.05). Furthermore, after excluding for age, gender, smoking status, and hypertension, logistic regression indicated that IS susceptibility of -607C carriers increased 1.6 times (OR = 1.601, 95%CI = 1.148-2.233, P = 0.006) compared to -607A carriers. Additionally, similar increases in IS risk were noted for male patients or patients less than 65 years old. In conclusion,IL-18 -607C/A (rs1946518) promoter polymorphism is associated with IS susceptibility, and the C allele may confer increased IS risk.

The impact of short daily hemodialysis on anemia and the quality of life in Chinese patients

Anemia is a frequent complication in hemodialysis patients. Compared to conventional hemodialysis (CHD), short daily hemodialysis (sDHD) has been reported to be effective in many countries except China. The aim of the present study was to determine whether sDHD could improve anemia and quality of life (QOL) for Chinese outpatients with end-stage renal disease. Twenty-seven patients (16 males/11 females) were converted from CHD to sDHD. All laboratory values were measured before conversion (baseline), at 3 months after conversion (sDHD1), and at 6 months after conversion (sDHD2). The patient's QOL was evaluated at baseline and 6 months after conversion using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). Hemoglobin concentration increased significantly from 107.4±7.9 g/L at baseline to 114.4±6.8 g/L (P<0.05) at sDHD1, and 118.3±8.4 g/L (P<0.001) at sDHD2 (Student paired t-test). However, the dose requirement for erythropoietin decreased from 6847.8±1057.3 U/week at baseline to 5869.6±1094.6 U/week (P<0.05) at sDHD2. Weekly stdKt/V increased significantly from 2.05±0.13 at baseline to 2.73±0.20 (P<0.001) at sDHD1, and 2.84±0.26 (P<0.001) at sDHD2. C-reactive protein decreased from baseline to sDHD1 and sDHD2, but without statistically significant differences. Physical and mental health survey scores increased in the 6 months following conversion to sDHD. sDHD may increase hemoglobin levels, decrease exogenous erythropoietin dose requirements, and improve QOL in Chinese hemodialysis patients compared to CHD. A possible mechanism for improvement of clinical outcomes may be optimized management of uremia associated with the higher efficiency of sDHD.

Randomized controlled trials of serotonin-norepinephrine reuptake inhibitor in treating major depressive disorder in children and adolescents: a meta-analysis of efficacy and acceptability

New generation antidepressant therapies, including serotonin-norepinephrine reuptake inhibitor (SNRIs), were introduced in the late 1980s; however, few comprehensive studies have compared the benefits and risks of various contemporary treatments for major depressive disorder (MDD) in young patients. A comprehensive literature search of PubMed, Cochrane, Embase, Web of Science, and PsycINFO databases was conducted from 1970 to January 2015. Only clinical trials that randomly assigned one SNRI or placebo to patients aged 7 to 18 years who met the diagnostic criteria for major depressive disorder were included. Treatment success, dropout rate, and suicidal ideation/attempt outcomes were measured. Primary efficacy was determined by pooling the risk ratios (RRs) of treatment response and remission. Acceptability was determined by pooling the RRs of dropouts for all reasons and for adverse effects as well as suicide-risk outcomes. Five trials with a total of 973 patients were included. SNRIs were not significantly more effective than placebo for treatment response but were for remission. The comparison of patients taking SNRIs that dropped out for all reasons and those taking placebo did not reach statistical significance. Significantly more patients taking SNRIs dropped out for adverse effects than those taking placebo. No significant difference was found in suicide-related risk outcomes. SNRI therapy does not display a superior efficacy and is not better tolerated compared to placebo in these young patients. However, duloxetine has a potential beneficial effect for depression in young populations, showing a need for further research.

Extraction optimization of antioxidant polysaccharides from leaves of Gynura bicolor (Roxb. & Willd.) DC

Orthogonal design was employed to study the effect of extraction time, temperature and liquid-to-solid ratio on the production of antioxidant polysaccharides from leaves of Gynura bicolor (PLG). Analysis of variance was performed on the data obtained. The most relevant variable was extraction time. A liquid-solid ratio of 30:1 (v/w), a temperature of 80 °C and an extraction time of 3 h were found to be optimal for PLG. The optimal extraction yield of 4.9% was obtained through additional verification test. Hydroxyl radical-scavenging activity, reducing power and ferrous ion chelating ability of PLG were determined. PLG possess concentration-dependent antioxidant potency and IC50 of PLG was 4.67, 0.24 and 4.31 mg/mL for hydroxyl radical-scavenging and ferric ion chelating abilities as well as reducing power, respectively. The results suggest that G. bicolor polysaccharides could be potential source of natural antioxidant and be contributor to the health benefits of G. bicolor.

La fórmula del cuerpo sin órganos una aproximación Bergsoniana a su enunciación

Tomada desde Artaud por Deleuze ya desde la redacción de Lógica del sentido (1969), la expresión de cuerpo sin órganos (CsO) no deja de causar al menos perplejidad. En su enunciación se traman puntos cruciales de la filosofía de Deleuze desde su teoría del acontecimiento y de la diferencia, pasando por una definición y una analítica del deseo, hasta una determinada noción de vida que articularía el proceso de su generación. Sin desestimar lo anterior y los profusos usos y determinaciones actuales que ha cobrado esta noción, nuestro propósito es vincular al CsO con la concepción de vida, que según nuestra lectura, se halla en la base de su formulación. Esto permanece en el texto como subyacente, y nuestra propuesta se inscribe en determinar el grado de influjo que posee el vitalismo de Bergson en la concepción de esta fórmula: desde este punto de vista es plausible sostener que el CsO es una operación que se funda de modo crucial en una lectura atenta al élan vital de bergsoniano. En suma, si el CsO es una involución creadora por definición de su proceso, no es sino porque su puesta en marcha significa y se efectúa en una constante y radical lucha que implica cada vez el desmontaje o desmembramiento de la idea de organismo.

A Destruktion heideggeriana da ontologia medieval em Die Grundprobleme Der Phänomenologie (§§ 10-12)

Em primeiro lugar, (1) examinarei a chamada Destruktion fenomenológica da ontologia medieval, componente básico do método a partir da história da ontologia. Nessa seção, coloco algumas questões sobre a apropriação da Idade Média com base na escolástica tardia, como se esta fosse o "cume" das reflexões precedentes! Em segundo lugar, (2) apresento a reflexão de próprio Heidegger sobre a ontologia medieval tal como se expõe no curso de semestre de verão de 1927 ("Os problemas fundamentais da fenomenologia"), ministrado na Universidade de Marburg. Igualmente nessa parte, faço algumas reflexões críticas sobre a leitura heideggeriana dos medievais, que se presta muito mais para conhecer o próprio modo de pensar de Heidegger do que os medievais em si mesmos, ou seja, pela leitura cursiva dos textos em seu contexto histórico e cultural: sem o élan espiritual, consubstancial aos escritos de Tomás de Aquino, por exemplo, a organização conceitual deste último não pareceria um sistema assaz grandioso e seco? Esta não terá sido a compreensão de Heidegger, fruto da separação metodológica feita entre mística medieval e filosofia escolástica desde o curso não proferido intitulado "Fundamentos filosóficos da Mística Medieval" (1918-1919)?