Cytotoxic lymphocytes in COPD airways: increased NK cells associated with disease,iNKT and NKT-like cells with current smoking

Background

Cytotoxic lymphocytes are increased in the airways of COPD patients. Whether this increase is driven primarily by the disease or by smoking is not clear, nor whether it correlates with the rate of decline in lung function.

Methods

Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study according to pre-determined criteria; 12 with COPD and a rapid decline in lung function (loss of FEV₁?≥?60?ml/year), 10 with COPD and a non-rapid decline in lung function (loss of FEV₁?≤?30?ml/year), 15 current and ex-smokers and 15 non-smokers with normal lung function. BAL lymphocyte subsets were determined using flow cytometry.

Results

In BAL fluid, the proportions of NK, iNKT and NKT-like cells all increased with pack-years. Within the COPD group, NK cells – but not iNKT or NKT-like cells – were significantly elevated also in subjects that had quit smoking. In contrast, current smoking was associated with a marked increase in iNKT and NKT-like cells but not in NK cells. Rate of lung function decline did not significantly affect any of the results.

Conclusions

In summary, increased proportions of NK cells in BAL fluid were associated with COPD; iNKT and NKT-like cells with current smoking but not with COPD. Interestingly, NK cell percentages did not normalize in COPD subjects that had quit smoking, indicating that these cells might play a role in the continued disease progression seen in COPD even after smoking cessation.

Trial registration

Clinicaltrials.gov identifier NCT02729220.

     

<Emphasis Type="Italic">Allophoma hayatii</Emphasis> sp. nov., an undescribed pathogenic fungus causing dieback of <Emphasis Type="Italic">Lantana camara</Emphasis> in Iran

Dieback and canker diseases are a major problem in ornamental shrubs and trees of Ahvaz, southwestern Iran. Symptomatic stems and branches were collected from two urban parks in the downtown regions of Ahvaz to identify the dieback-causing agents of Lantana camara. Accordingly, two isolates of a new species, Allophoma hayatii sp. nov., were obtained, which are described and illustrated. This species is identified based on morphological characters and analyses of nucleotide sequences of four regions, including internal transcribed spacer 1 and 2 and 5.8S nrDNA (ITS), partial large subunit 28S nrDNA (LSU-D1/D2), a partial sequence of the β-tubulin (tub2) and part of the RNA polymerase II (rpb2). The isolates of A. hayatii generated a well-supported clade in the trees constructed from multi-locus phylogenetic analysis, distinct from other previously known species of Allophoma. Pathogenicity of both isolates was verified by the inoculation of stem fragments of L. camara. These findings confirm A. hayatii as the causal agents of dieback and canker of L. camara in Ahvaz.     

Calcium: A novel and efficient inducer of differentiation of adipose‐derived stem cells into neuron‐like cells

This study comparatively investigated the effectiveness of calcium and other well‐known inducers such as isobutylmethylxanthine (IBMX) and insulin in differentiating human adipose‐derived stem cells (ADSCs) into neuronal‐like cells. ADSCs were immunophenotyped and differentiated into neuron‐like cells with different combinations of calcium, IBMX, and insulin. Calcium mobilization across the membrane was determined. Differentiated cells were characterized by cell cycle profiling, staining of Nissl bodies, detecting the gene expression level of markers such as neuronal nuclear antigen (NeuN), microtubule associated protein 2 (MAP2), neuron‐specific enolase (NSE), doublecortin, synapsin I, glial fibrillary acidic protein (GFAP), and myelin basic protein (MBP) by quantitative real‐time polymerase chain reaction (quantitative real‐time polymerase chain reaction (qRT‐PCR) and protein level by the immunofluorescence technique. Treatment with Ca + IBMX + Ins induced neuronal appearance and projection of neurite‐like processes in the cells, accompanied with inhibition of proliferation and halt in the cell cycle. A significantly higher expression of MBP, GFAP, NeuN, NSE, synapsin 1, doublecortin, and MAP2 was detected in differentiated cells, confirming the advantages of Ca + IBMX + Ins to the other combinations of inducers. Here, we showed an efficient protocol for neuronal differentiation of ADSCs, and calcium fostered differentiation by augmenting the number of neuron‐like cells and instantaneous increase in the expression of neuronal markers.     

Enhancement of muscarinic receptor-coupled phosphatidyl inositol hydrolysis in diabetic bladder

We previously have shown an increase in muscarinic receptor density in streptozotocin (STZ)-induced diabetic and sucrosefed diuretic rat detrusor that correlates with an increase in the contractile response to muscarinic agonist (J Pharmacol Exp Ther 248: 81, 1989; Diabetes 40: 265, 1991). To investigate the signal transduction pathway involved in this altered functional response, we examined muscarinic receptor-coupled phosphatidylinositol metabolism in STZ-diabetic, sucrose-fed diuretic and age-matched control rat bladders. [³H]myo-inositol uptake was similar in all groups, but incorporation of myo-inositol into phosphatidylinositol (PI) was significantly increased in the diabetic bladder compared to the sucrose-fed and control rat bladders. Carbachol-induced increase in inositol phosphate (IPs) production was higher in the diabetic bladder than in bladders from control and sucrose-fed animals although the EC₅₀ values were similar for all groups. Enhanced inositol phosphate production after muscarinic agonist stimulation may be due not only to the upregulation of muscarinic receptors but also to the increased incorporation of myo-inositol into PI in the STZ-induced diabetic bladder.     

An information-based machine learning approach to elasticity imaging

An information-based technique is described for applications in mechanical property imaging of soft biological media under quasi-static loads. We adapted the Autoprogressive method that was originally developed for civil engineering applications for this purpose. The Autoprogressive method is a computational technique that combines knowledge of object shape and a sparse distribution of force and displacement measurements with finite-element analyses and artificial neural networks to estimate a complete set of stress and strain vectors. Elasticity imaging parameters are then computed from estimated stresses and strains. We introduce the technique using ultrasonic pulse-echo measurements in simple gelatin imaging phantoms having linear-elastic properties so that conventional finite-element modeling can be used to validate results. The Autoprogressive algorithm does not require any assumptions about the material properties and can, in principle, be used to image media with arbitrary properties. We show that by selecting a few well-chosen force–displacement measurements that are appropriately applied during training and establish convergence, we can estimate all nontrivial stress and strain vectors throughout an object and accurately estimate an elastic modulus at high spatial resolution. This new method of modeling the mechanical properties of tissue-like materials introduces a unique method of solving the inverse problem and is the first technique for imaging stress without assuming the underlying constitutive model.     

Targeted-nanoliposomal combretastatin A4 (CA-4) as an efficient antivascular candidate in the metastatic cancer treatment

A number of antiangiogenic drugs have been approved by the Food and Drug Administration which are used in cancer therapy, and variety of other agents in several stages of clinical development or in preclinical assessment. Among these, combretastatin A4 (CA-4) is an under-researched inhibitor of angiogenesis that shows potential activity in the treatment of advanced tumors with migration capacity. However, its clinical application has been limited due to poor water solubility, low bioavailability, rapid metabolism, and systemic elimination. During the last decade, numerous investigations have been done to overcome these problems by using different CA-4 delivery systems or developing produgs of CA-4 or its structural analogs. Nevertheless, these strategies could not be efficient out of the undesired side effects on normal tissues. Nanoliposomal CA-4 not only benefits from the advantage of using liposomal drugs as opposed to free drugs but also can accumulate in the tumor site via specific targeting ligands, which leads to efficient targeting and enhancement of bioavailability. To the best of our knowledge, we consider an important attempt to understand different factors that might influence the CA-4 loading and release pattern of liposomes and the consequent results in tumor therapy. In this review, we shed light on various studied liposomal CA-4 formulations showing application thereof in cancer treatment.     

Patterns of Evolution in Iranian Tribal Textiles

Ever since the publication of The Origin of Species, anthropologists and archaeologists have been in turns enchanted and repulsed by the idea that cultural diversity can be explained by a Darwinian model of descent with modification. Over the last decade, this debate has intensified following the publication of a number of studies that have sought to reconstruct cultural histories using modern computational methods of phylogenetic analysis imported from biology. In this paper, I focus on evolution of tribal textile assemblages in Iran and Central Asia. Using cladistic phylogenetic analysis, I show that similarities and differences among the assemblages can be largely explained in terms of descent with modification from ancestral assemblages. Interestingly, the phylogenetic signal in design characters is just as strong (if not stronger) than the signal in technical characters. This may seem surprising given that techniques, like genes, are transmitted “vertically” from mothers to daughters whereas designs are frequently transmitted “horizontally” among peers. However, a closer examination reveals that the transmission of designs between weavers mainly occurs within, rather than between groups, and that, as in many cultures past and present, there are important constraints on the latter. This highlights that differences in the ways in which genes and cultural traits are transmitted among individuals should not be assumed to lead to differences in macro-level patterns of evolution, as many archaeologists and anthropologists have supposed.     

The Effect of Leptin on Sex Hormones and Antioxidant Enzyme Levels in Obese and Normal Male Rats

International Journal of Peptide Research and Therapeutics - The correlation between leptin, nutritional status and reproductive performance is known but its effect on male obese is not fully...