Cross-regulation of CD86 by CD80 differentially regulates T helper responses from Mycobacterium tuberculosis secretory antigen-activated dendritic cell subsets

We report that stimulation of Mycobacterium tuberculosis secretory antigen- and tumor necrosis factor alpha-matured BALB/c mouse bone marrow dendritic cells (BMDCs) with anti-CD80 monoclonal antibody up-regulated CD86 levels on the cell surface. Coculture of these BMDCs with na?ve, allogeneic T cells now down-regulated T helper cell type 1 (Th1) responses and up-regulated suppressor responses. Similar results were obtained with splenic CD11c(+)/CD8a(-) DCs but not to the same extent with CD11c(+)/CD8a(+) DCs. Following coculture with T cells, only BMDCs and CD11c(+)/CD8a(-) DCs and not CD11c(+)/CD8a(+) DCs displayed increased levels of surface CD86, and further, coculturing these DCs with a fresh set of T cells attenuated Th1 responses and increased suppressor responses. Not only na?ve but even antigen-specific recall responses of the Th1-committed cells were modulated by DCs expressing up-regulated surface CD86. Further analyses showed that stimulation with anti-CD80 increased interleukin (IL)-10 and transforming growth factor-beta-1 levels with a concomitant reduction in IL-12p40 and interferon-gamma levels from BMDCs and CD11c(+)/CD8a(-) DCs and to a lesser extent, from CD11c(+)/CD8a(+) DCs. These results suggest that cross-talk between costimulatory molecules differentially regulates their relative surface densities leading to modulation of Th responses initiated from some DC subsets, and Th1-committed DCs such as CD11c(+)/CD8a(+) DCs may not allow for such modulation. Cognate antigen-presenting cell (APC):T cell interactions then impart a level of polarization on APCs mediated via cross-regulation of costimulatory molecules, which govern the nature of subsequent Th responses.     

The role of IL-1β during human immunodeficiency virus type 1 infection

Interleukin (IL)-1β is a key innate cytokine that is essential for immune activation and promoting the inflammatory process. However, abnormal elevation in IL-1β levels has been associated with unwanted clinical outcomes. IL-1β is the most extensively studied cytokine among the IL-1 family of cytokines and its role in pathology is well established. During the course of human immunodeficiency virus type 1 (HIV-1) infection, the level of this proinflammatory cytokine is increased in different anatomical compartments, particularly in lymphatic tissues, and this elevation is associated with disease progression. The aim of this review is to address the pathological roles play by IL-1β in the light of enhancing HIV-1 replication, driving immune cell depletion, and chronic immune activation. The role of IL-1β in HIV-1 transmission (sexually or vertically ‘from mother-to-child’) will also be discussed. Additionally, the impact of the available antiretroviral therapy regimens on the levels of IL-1β in HIV-1 treated patients is also discussed. Finally, we will provide a glance on how IL-1β could be targeted as a therapeutic strategy.     

Effect of muscle activity immediately after botulinum toxin injection for writer's cramp.

Animal and human studies have shown that nerve stimulation enhances some effects of botulinum toxin (btx A) injection. Voluntary muscle activity might work similarly and would focus the effect of an injection into the active muscles. We studied the effects of exercise immediately after btx A injection in eight patients with writer's cramp with established response to btx A over two injection cycles with a single-blinded, randomized, crossover design. Immediately after the first study injection, they were randomly assigned to write continuously for 30 min or have their hand and forearm immobilized for 30 min. Following the second injection, they were assigned the alternate condition. Patients were assessed just before each injection, and at 2 weeks, 6 weeks, and 3 months post-injection. Assessment included objective strength testing, self-reported rating of benefit and weakness, and blinded evaluation of videotapes and writing samples of the patients writing a standard passage. Strength testing showed that the maximum weakness occurred at 2 weeks post-injection, but the benefit was maximum at 6 weeks post-injection. The "write" condition resulted in greater reduction in strength than the "rest" condition. Btx A treatment led to improvement in self-reported ratings, writer's cramp rating scale scores by blinded raters, and reduction in writing time, but the differences between the "write" and "rest" conditions were not significant. We conclude that voluntary muscle activity immediately after btx A injection leads to greater reduction in muscle strength. Our findings raise the possibility that voluntary muscle activation may allow reduction of btx A doses and favorably alter the balance of benefit and side effects of btx A injections.     

Water immersion increases urinary excretion of aquaporin-2 in healthy humans

Many previous studies have shown that aquaporin-2 (AQP2), the vasopressin-regulated water channel, is excreted in the urine and that the excretion increases in response to vasopressin. Moreover, recently a close correlation between AQP2 excretion in urine and kidney AQP2 expression has been demonstrated, showing that urinary excretion of AQP2 is a reliable indicator for AQP-2 function. As head-out water immersion causes an expansion in the central vascular volume equal to that induced by 2 liters of saline, without modifying plasma composition, we used immersion in water to evaluate if the response to acute expansion of the central vascular volume could involve vasporessin (AVP) and AQP2. In healthy subjects, concentrations of plasma atrial natriuretic factor (ANF) and AVP, and urinary AQP2 were measured during a 2-hour immersion period. In all subjects, immersion caused a prompt and marked increase in immunoreactive ANF (23.0 +/- 2.12 pg/ml at second hour vs. 2.17 +/- 0.42 pg/ml at baseline) and in urinary excretion of AQP2 (23.9 +/- 2. 69 pmol/mg creatinine at second hour vs. 4.42 +/- 0.14 pmol/mg creatinine at baseline), while a significant decrease was found in plasma AVP. Recovery was associated with a prompt return to pre-study levels. These findings demonstrate that heat-out water immersion stimulates urinary excretion of AQP2 in absence of an increase in plasma AVP.     

Diagnosis of the multiple effect of selenium nanoparticles decorated by Asteriscus graveolens components in inhibiting HepG2 cell proliferation

Using plant bio-components for Designing green metal nanoparticles was considered as one of the most important methods in nanomedical application field due to their eco-friendly, cheap source, easily obtainable and having a high detection result. In this report, we fabricated eco-friendly engineering and cost-effective technique for green selenium nanoparticles from 0.01 M H₂SeO₃ solution using Asteriscus graveolens leaves extract as reducing and a capping agent at ambient temperature. Spectral techniques have been used to identify the formatted Selenium nanoparticles such as UV–Vis, pH, XPs, FT-IR, XRD, LDS, Z.P, EDS, TEM and AFM spectroscopy, which showed a size of 20 nm with spherical shape. Herein, the multi-effect of decorated Se-NPs surface have been evaluated, firstly on the hemolysis that showed completely hemocompatibility. Cytotoxicity assay showed that Se-NPs have a high selective effect on the HepG2 apoptosis and which proved by phase-contrast microscopy. Furthermore, the effect of nanoparticles on the action of the mechanism internal revealed that Se-NPs significantly and rapidly increased the level of reactive oxygen species and lipid peroxidation, while caused decreased the potential of mitochondrial membrane and glutathione level, which they together responsible on regulating the HepG2 cells fate. Furthermore, Flow cytometry analysis gave high values about S and G2/M phases of cell cycle resulting from Se-NPs effectiveness. In the end, with all the recorded information that has been measured in this study, this report provides a suitable and effective pathway for the green fabrication of Se-NPs decorated by biomolecules having high anticancer inhibited.     

Changes in body weight and physical performance after receiving dietary advice in patients with chronic obstructive pulmonary disease (COPD): 1-year follow-up

Nutritional studies in patients with chronic obstructive pulmonary disease (COPD) are often based on oral nutritional supplementation and are of short duration. Our aim was to study the changes in body weight and physical performance in COPD patients after receiving the dietary advice for 1 year. Thirty-six patients with COPD as a primary diagnosis (mean age: 68.5 ± 7.8 years), referred to a pulmonary rehabilitation program were studied. Each patient received dietary advice individually. Body weight had increased significantly by 1.3 kg (p = 0.02) and walking distance by 83.2 m (p = 0.007) after 1 year. There was an increase in mean handgrip strength after 1 year (1.6 kg, p = 0.07). The mean intake of energy and protein expressed as percent of energy and protein requirement had increased after 1 year (15%, p < 0.001, and 5.6%, p = 0.09, respectively). Handgrip strength correlated significantly with energy (r = 0.53, p = 0.002), fat (r = 0.50, p = 0.02) and protein intake (r = 0.41, p = 0.002) after 1 year. In conclusion, positive effects on body weight, handgrip strength and walking distance in patients with COPD were seen after receiving dietary advice with a 1-year follow-up.     

Detecting EGFR alterations in clinical specimens—pitfalls and necessities

We investigated the epidermal growth factor receptor (EGFR) status in early stage lung cancer in Southern Sweden, a population for which there are no previous reports on the EGFR mutation frequency. Three hundred fifty small cell lung cancers, adenocarcinomas (AC), squamous cell carcinomas (SqCC), and large cell carcinomas were analyzed using a combination of techniques for the analysis of protein expression, gene copy numbers, and mutations. Immunohistochemical (IHC) staining with antibodies for the EGFR mutations L858R and del E746-A750 revealed intratumoral heterogeneity and several discrepant cases when compared to mutation-specific polymerase chain reaction (PCR)-based analysis. The frequencies of these two mutations, when considering IHC staining with mutation-specific antibodies in a cohort of 298 cases and subsequent confirmation by PCR, were 10 % in AC and <2 % in SqCC. Furthermore, screening by sequencing of EGFR in a cohort of 52 lung AC and squamous carcinomas demonstrated a more diverse mutation spectrum, not covered by the mutation-specific antibodies. High expression of total EGFR protein was correlated to high gene copy numbers but did not reflect the mutational status of the tumors. We believe that the mutation spectra in a Southern Swedish population is too diverse to be covered by the mutation-specific antibodies, and we also raise some other issues regarding the use of the mutation-specific antibodies, for example concerning heterogeneous expression of the mutated protein, optimal antibody dilution, and discrepancies between staining results and PCR.