Recent developments in antibacterial and antifungal chitosan and its derivatives.

http://www.wanglab-tsinghua.com/pdf/2013PMS_321.pdf

Electro-spinning/netting: A strategy for the fabrication of three-dimensional polymer nano-fiber/nets

Cell motility is central to tissue homeostasis in health and disease, and there is hardly any cell in the body that is not motile at a given point in its life cycle. Important physiological processes intimately related to the ability of the respective cells to migrate include embryogenesis, immune defense, angiogenesis, and wound healing. On the other side, migration is associated with life-threatening pathologies such as tumor metastases and atherosclerosis. Research from the last ∼15 years revealed that ion channels and transporters are indispensable components of the cellular migration apparatus. After presenting general principles by which transport proteins affect cell migration, we will discuss systematically the role of channels and transporters involved in cell migration.

https://www.physiology.org/doi/pdf/10.1152/physrev.00018.2011

Role of Ion Channels and Transporters in Cell Migration

BCR-ABL tyrosine kinase inhibitors in the treatment of Philadelphia chromosome positive chronic myeloid leukemia: a review.

Targeted therapy in the form of selective tyrosine kinase inhibitors (TKI) has transformed the approach to management of chronic myeloid leukemia (CML) and dramatically improved patient outcome to the extent that imatinib is currently accepted as the first-line agent for nearly all patients presenting with CML, regardless of the phase of the disease. Impressive clinical responses are obtained in the majority of patients in chronic phase; however, not all patients experience an optimal response to imatinib, and furthermore, the clinical response in a number of patients will not be sustained. The process by which the leukemic cells prove resistant to TKIs and the restoration of BCR-ABL1 signal transduction from previous inhibition has initiated the pursuit for the causal mechanisms of resistance and strategies by which to surmount resistance to therapeutic intervention. ABL kinase domain mutations have been extensively implicated in the pathogenesis of TKI resistance, however, it is increasingly evident that the presence of mutations does not explain all cases of resistance and does not account for the failure of TKIs to eliminate minimal residual disease in patients who respond optimally. The focus of exploring TKI resistance has expanded to include the mechanism by which the drug is delivered to its target and the impact of drug influx and efflux proteins on TKI bioavailability. The limitations of imatinib have inspired the development of second generation TKIs in order to overcome the effect of resistance to this primary therapy. (Clin Cancer Res 2009;15(24):7519-27).

https://clincancerres.aacrjournals.org/content/clincanres/15/24/7519.full.pdf

Mechanisms of Resistance to Imatinib and Second-Generation Tyrosine Inhibitors in Chronic Myeloid Leukemia.

Chitosan (0.1 g l−1), assayed in a simple medium, reduced the viability of four lactic acid bacteria isolated during the beer production process by 5 logarithmic cycles, whereas activity against seven commercial brewing yeasts required up to 1 g chitosan l−1. Antimicrobial activity was inversely affected by the pH of the assay medium. In brewery wort, chitosan (0.1 g l−1) selectively inhibited bacterial growth without altering yeast viability or fermenting performance.

Selective antimicrobial activity of chitosan on beer spoilage bacteria and brewing yeasts

Imatinib resistance in multidrug-resistant K562 human leukemic cells.

Cell migration/proliferation processes associated with wound healing were measured in BeWo cells at 6 h, when mitosis is still scarce. Cells were cultured in medium with 1% fetal bovine serum to minimize proliferation. BeWo cell migration covered 20.6 ± 7.0%, 38.0 ± 5.4%, 16.6 ± 4.8% and 13.7 ± 3.6% of the wound when cultivated under control, aldosterone (100 nM, 12 h), aldosterone plus amiloride (10 μM) and amiloride treatments, respectively. When BeWo cells were treated with aldosterone, there was an increase in wound healing (P < 0.05), which was prevented by adding the ENaC blocker amiloride (P < 0.05, n = 16). Immunocytochemistry studies showed that the three ENaC subunits showed greater expression at the leading edge of the wound 3 h after injury, supporting the notion that these proteins participate in a postinjury signal. Antisense oligonucleotides directed against the α-ENaC subunit decreased the migratory response of the cells compared to the sense treated cells or the cells without oligonucleotides (P < 0.001, n = 16): 30.2 ± 3.7%, 17.6 ± 1.3%, 27.5 ± 1.5% and 20.2 ± 1.5% reinvasion of the wound with aldosterone, aldosterone plus antisense, aldosterone plus sense treatments and control conditions, respectively. Aldosterone and amiloride influence wound healing in BeWo cells, probably by their effects upon ENaCs, transmitting a signal to the cell cytoplasm for the release of several agents that promote cell migration.

Cell Migration in BeWo Cells and the Role of Epithelial Sodium Channels

The present study was performed to assay sodium currents in BeWo cells. These cells comprise a human trophoblast cell line which displays many of the biochemical and morphological properties similar to those reported for the in uterus proliferative cytotrophoblast. For whole-cell patch-clamp experiments, BeWo cells treated for 12 h with 100 nM aldosterone were exposed to 8Br-cAMP, a membrane-permeable cAMP analogue, to induce channel activity. Cells showed an amiloride-sensitive ion current (IC50 of 5.77 μM). Ion substitution experiments showed that the amiloride-sensitive current carried cations with a permeability rank order of Li+ > Na+ > K+ > NMDG (PLi/PNa = 1.3, PK/PNa = 0.6, PNMDG/PNa = 0.2). In cells pretreated with aldosterone, we observed that nearly half of successful patches had sodium channels with a linear conductance of 6.4 ± 1.8 pS, a low voltage-independent P
 o and a PK/PNa of 0.19. Using RT-PCR, we determined that control cells express the α-, but not β- and γ-, epithelial sodium channel (ENaC) mRNA. When cells were treated with aldosterone (100 nM, 12 h), all α-, β- and γ-ENaC mRNAs were detected. The presence of ENaC subunit proteins in these cells was confirmed by Western blot analysis and immunolocalization with specific ENaC primary antibodies. In summary, our results suggest that BeWo cells express ENaC subunits and that aldosterone was able to modulate a selective response by generating amiloride-sensitive sodium currents similar to those observed in other human tissues.

Epithelial Sodium Channel in a Human Trophoblast Cell Line (BeWo)

The syncytiotrophoblast (SCT), a multinucleated epithelium forming the outer layer of chorionic villi, acts in human placenta as a transporting barrier regulating the transference of nutrients, solutes and water between maternal and fetal blood. Electrolyte homeostasis and extracellular fluid volume are maintained primarily by regulated Na+ transport. The present study was conducted to analyze the presence of the epithelial Na channel (ENaC) in placental tissue from normal and pre-eclamptic women and in BeWo cell, a model of a human SCT. Changes in the expression of these proteins during sodium transport across the placenta may be related to the pathogeny of pre-eclampsia. The role that ENaC and Na+ transport deregulation play on human placental tissues still remains unknown although in aldosterone-responsive epithelial cells (kidney, colon), abnormalities upregulating its activity lead to increased Na+ uptake and hypertension (i.e. Liddle's syndrome) whereas a diminished channel activity can result in the pseudohypoaldosteronisn syndrome with salt loss and hypotension. Our results show that ENaC is expressed in the apical membrane of normal syncytiotrophoblast. The amplified fragment of alpha-ENaC was cloned and sequenced having a 100% identity with the sequence of (alpha-ENaC obtained from GenBank (SCNN1A, accession number Z92981). We found that the transcription of the alpha-ENaC mRNA was not detectable in preeclamptic placentas and the protein was not observed with immunohistochemistry staining, probably indicating a low protein expression level. In BeWo cells ENac was found and its expression is regulated by aldosterone, vasopressin, progesterone and estradiol. With patch clamp techniques we studied the currents trough ENaO channels in Bewo cells. We observed currents that were blocked by 10 microM amiloride in cells incubated in 100 nM aldosterone for 12 hs. The amplitude of this current was 20-fold the basal current, a reversal potential of 3 mV and a conductance of 127 +/- 26 pS/pF with pulses between -60 and -140 mV. These characteristics are similar to those reported in ENaC channels in several tissues. Although their roles in placenta are still poorly understood, the differences in the expression of ENaC in pre-eclamptic placentas may have consequences for ion transport and these data could lead to future studies concerning the mechanism involved in the pathophysiology of pre-eclampsia.

Silvana del Mónaco

Papers

Selective antimicrobial activity of chitosan on beer spoilage bacteria and brewing yeasts

Imatinib resistance in multidrug-resistant K562 human leukemic cells.

Cell Migration in BeWo Cells and the Role of Epithelial Sodium Channels

Epithelial Sodium Channel in a Human Trophoblast Cell Line (BeWo)

[Characterization of the epithelial sodium channel in human pre-eclampsia syncytiotrophoblast].