Evaluating bronchodilator effects in chronic obstructive pulmonary disease using diffusion-weighted hyperpolarized helium-3 magnetic resonance imaging

The objective of this study was to evaluate the regional effects of bronchodilator administration in chronic obstructive pulmonary disease (COPD) using hyperpolarized helium-3 ((3)He) MRI apparent diffusion coefficient (ADC). Ten COPD ex-smokers provided written, informed consent and underwent diffusion-weighted, hyperpolarized (3)He MRI, spirometry, and plethysmography before and 25 ± 2 min after bronchodilator administration. Pre- and postsalbutamol whole-lung (WL) ADC maps were generated and registered together to identify the lung regions containing the (3)He signal at both time points, and mean ADC within those regions of interest (ROI) was determined for a measurement of previously ventilated ROI ADC (ADC(P)). Lung ROI with (3)He signal at both time points was used as a binary mask on postsalbutamol WL ADC maps to obtain an ADC measurement for newly ventilated ROI (ADC(N)). Postsalbutamol, no significant differences were detected in WL ADC (P = 0.516). There were no significant differences between ADC(N) and ADC(P) postsalbutamol (P = 1.00), suggesting that the ADC(N) lung regions were not more emphysematous than the lung ROI participating in ventilation before bronchodilator administration. Postsalbutamol, a statistically significant decrease in ADC(P) (P = 0.01) was detected, and there were significant differences between ADC(P) in the most anterior and most posterior image slices (P = 0.02), suggesting a reduction in regional gas trapping following bronchodilator administration. Regional evaluation of tissue microstructure using hyperpolarized (3)He MRI ADC provides insights into lung alterations that accompany improvements in regional (3)He gas distribution after bronchodilator administration.     

Novel mass spectrometry imaging software assisting labeled normalization and quantitation of drugs and neuropeptides directly in tissue sections

MALDI MS imaging has been extensively used to produce qualitative distribution maps of proteins, peptides, lipids, small molecule pharmaceuticals and their metabolites directly in biological tissue sections. There is growing demand to quantify the amount of target compounds in the tissue sections of different organs. We present a novel MS imaging software including protocol for the quantitation of drugs, and for the first time, an endogenous neuropeptide directly in tissue sections. After selecting regions of interest on the tissue section, data is read and processed by the software using several available methods for baseline corrections, subtractions, denoising, smoothing, recalibration and normalization. The concentrations of in vivo administered drugs or endogenous compounds are then determined semi-automatically using either external standard curves, or by using labeled compounds, i.e., isotope labeled analogs as standards. As model systems, we have quantified the distribution of imipramine and tiotropium in the brain and lung of dosed rats. Substance P was quantified in different mouse brain structures, which correlated well with previously reported peptide levels. Our approach facilitates quantitative data processing and labeled standards provide better reproducibility and may be considered as an efficient tool to quantify drugs and endogenous compounds in tissue regions of interest.     

Foliar Spray with 24-Epibrassinolide Enhanced Strawberry Fruit Quality,Phytochemical Content,and Postharvest Life

Journal of Plant Growth Regulation - Activation of complex metabolic pathways and antioxidant activities is necessary for enhancing quality and health promoting capacity of food crops. Plant growth...     

IL-35, a double-edged sword in cancer

Interleukin 35 (IL-35), a cytokine mainly produced by regulatory T cells (Treg cells), is composed of an Epstein-Barr virus–induced gene 3 β-chain and an IL-12 p35 α-chain. IL-35 causes tumorigenicity in cancer, protects cancer cells against apoptosis, and facilitates cancer progression. However, a few reports have referred to its contradictory roles in cancer prevention. Therefore, the exact purpose of this cytokine in cancer development has become a fundamental question that needs to be answered. In this review, we explain the structure of IL-35 and its receptors and their different signaling pathways. Finally, the function of IL-35 in some cancers and the possible application of this cytokine in approaches for cancer therapy have been discussed.     

H. pylori‐Induced Apoptosis in Human Gastric Cancer Cells Mediated via the Release of Apoptosis‐Inducing Factor from Mitochondria

Background and Aim: Our previous study of Helicobacter pylori‐induced apoptosis showed the involvement of Bcl‐2 family proteins and cytochrome c release from mitochondria. Here, we examine the release of other factors from mitochondria, such as apoptosis‐inducing factor (AIF), and upstream events involving caspase‐8 and Bid. Methods: Human gastric adenocarcinoma (AGS) cells were incubated with a cagA‐positive H. pylori strain for 0, 3, 6, and 24 hours and either total protein or cytoplasmic, nuclear, and mitochondrial membrane fractions were collected. Results: Proteins were immunoblotted for AIF, Bid, polyadenosine ribose polymerase (PARP), caspase‐8, and β‐catenin. H. pylori activated caspase‐8, caused PARP cleavage, and attenuated mitochondrial membrane potential. A time‐dependent decrease in β‐catenin protein expression was detected in cytoplasmic and nuclear extracts, coupled with a decrease in β‐actin. An increase in the cytoplasmic pool of AIF was seen as early as 3 hours after H. pylori exposure, and a concomitant increase was seen in nuclear AIF levels up to 6 hours. A band corresponding to full‐length Bid was seen in both the cytoplasmic and the nuclear fractions of controls, but not after H. pylori exposure. Active AIF staining was markedly increased in gastric mucosa from infected persons, compared to uninfected controls. Conclusion: H. pylori might trigger apoptosis in AGS cells via interaction with death receptors in the plasma membrane, leading to the cleavage of procaspase‐8, release of cytochrome c and AIF from mitochondria, and activation of subsequent downstream apoptotic events, as reported previously for chlorophyllin. This is consistent with AIF activation that was found in the gastric mucosa of humans infected with H. pylori. Hence, the balance between apoptosis and proliferation in these cells may be altered in response to injury caused by H. pylori infection, leading to an increased risk of cancer.     

Towards a better understanding of the Chenopodium album aggregate (Amaranthaceae) in the Middle East: A karyological,cytometric and morphometric investigation

The study of variation in nuclear genome size, especially when combined with common garden experiments, significantly contributes to disentangling interspecies relationships within taxonomically complicated plant groups. The Chenopodium album aggregate is among the morphologically most variable groups and consists of many weakly differentiated cosmopolitan entities. We analysed nuclear genome size variation in diploid and polyploid species of the aggregate from Iran using flow cytometry of 282 accessions from 88 populations of 7 species. To this end, we also determined chromosome numbers and performed a morphometric study to reveal the extent of intraspecific morphological variation. We found that Iranian species are exclusively diploid (C. vulvaria), tetraploid (C. novopokrovskyanum, C. strictum, C. sosnowskyi and C. chaldoranicum) or hexaploid (C. album subsp. album, C. album subsp. iranicum and C. opulifolium). Six homogeneous relative genome size groups were distinguished among the species studied. Our morphometric study surprisingly revealed that under similar ecological conditions Chenopodium species are morphologically stable and well distinguishable, exhibited very little morphological variation. Hence, immense variation in leaf shapes, branching and inflorescence organization seen in the field has not been repeated under greenhouse conditions. The only exception was C. album s. str. which exhibited numerous morphotypes, covering the variation of remaining species.     

Automatic quantification of microscopic heart damage in a mouse model of Duchenne muscular dystrophy using optical polarization tractography

Quantification of microscopic myocardium damage in a diseased heart is important in studying disease progression and evaluating treatment outcome. However, it is challenging to use traditional histology and existing medical imaging modalities to quantify all microscopic damages in a small animal heart. Here, a method was developed for fast visualization and quantification of focal tissue damage in the mouse heart based on the fiber alignment index of the local myofiber organization obtained in optical polarization tractography (OPT). This method was tested in freshly excised hearts of the mdx4cv mouse, a commonly used mouse model for studying Duchenne cardiomyopathy. The hearts of age‐matched C57BL/6 mice were also imaged as the normal controls. The results revealed a significant amount of damage in the mdx4cv hearts. Histology comparisons confirmed the damage identified by OPT. This fast and automatic method may greatly enhance preclinical studies in murine models of heart diseases.