Electrospun fibers based on porcine plasma: a rheological and morphological study

Iranian Polymer Journal - The present work focuses on the assessment of the ability of porcine plasma protein (PPP) to be electrospun satisfactorily to form fibre mats, and their rheological and...     

Target Score—A Proteomics Data Selection Tool Applied to Esophageal Cancer Identifies GLUT1-Sialyl Tn Glycoforms as Biomarkers of Cancer Aggressiveness

Esophageal cancer (EC) is a life-threatening disease, demanding the discovery of new biomarkers and molecular targets for precision oncology. Aberrantly glycosylated proteins hold tremendous potential towards this objective. In the current study, a series of esophageal squamous cell carcinomas (ESCC) and EC-derived circulating tumor cells (CTCs) were screened by immunoassays for the sialyl-Tn (STn) antigen, a glycan rarely expressed in healthy tissues and widely observed in aggressive gastrointestinal cancers. An ESCC cell model was glycoengineered to express STn and characterized in relation to cell proliferation and invasion in vitro. STn was found to be widely present in ESCC (70% of tumors) and in CTCs in 20% of patients, being associated with general recurrence and reduced survival. Furthermore, STn expression in ESCC cells increased invasion in vitro, while reducing cancer cells proliferation. In parallel, an ESCC mass spectrometry-based proteomics dataset, obtained from the PRIDE database, was comprehensively interrogated for abnormally glycosylated proteins. Data integration with the Target Score, an algorithm developed in-house, pinpointed the glucose transporter type 1 (GLUT1) as a biomarker of poor prognosis. GLUT1-STn glycoproteoforms were latter identified in tumor tissues in patients facing worst prognosis. Furthermore, healthy human tissues analysis suggested that STn glycosylation provided cancer specificity to GLUT1. In conclusion, STn is a biomarker of worst prognosis in EC and GLUT1-STn glycoforms may be used to increase its specificity on the stratification and targeting of aggressive ESCC forms.     

Ivabradine Induces Cardiac Protection against Myocardial Infarction by Preventing Cyclophilin-A Secretion in Pigs under Coronary Ischemia/Reperfusion

In response to cardiac ischemia/reperfusion, proteolysis mediated by extracellular matrix metalloproteinase inducer (EMMPRIN) and its secreted ligand cyclophilin-A (CyPA) significantly contributes to cardiac injury and necrosis. Here, we aimed to investigate if, in addition to the effect on the funny current (I(f)), Ivabradine may also play a role against cardiac necrosis by reducing EMMPRIN/CyPA-mediated cardiac inflammation. In a porcine model of cardiac ischemia/reperfusion (IR), we found that administration of 0.3 mg/kg Ivabradine significantly improved cardiac function and reduced cardiac necrosis by day 7 after IR, detecting a significant increase in cardiac CyPA in the necrotic compared to the risk areas, which was inversely correlated with the levels of circulating CyPA detected in plasma samples from the same subjects. In testing whether Ivabradine may regulate the levels of CyPA, no changes in tissue CyPA were found in healthy pigs treated with 0.3 mg/kg Ivabradine, but interestingly, when analyzing the complex EMMPRIN/CyPA, rather high glycosylated EMMPRIN, which is required for EMMPRIN-mediated matrix metalloproteinase (MMP) activation and increased CyPA bonding to low-glycosylated forms of EMMPRIN were detected by day 7 after IR in pigs treated with Ivabradine. To study the mechanism by which Ivabradine may prevent secretion of CyPA, we first found that Ivabradine was time-dependent in inhibiting co-localization of CyPA with the granule exocytosis marker vesicle-associated membrane protein 1 (VAMP1). However, Ivabradine had no effect on mRNA expression nor in the proteasome and lysosome degradation of CyPA. In conclusion, our results point toward CyPA, its ligand EMMPRIN, and the complex CyPA/EMMPRIN as important targets of Ivabradine in cardiac protection against IR.     

Ethylene and Nitric Oxide Involvement in the Regulation of Fe and P Deficiency Responses in Dicotyledonous Plants

Iron (Fe) and phosphorus (P) are two essential elements for plant growth. Both elements are abundant in soils but with poor availability for plants, which favor their acquisition by developing morphological and physiological responses in their roots. Although the regulation of the genes related to these responses is not totally known, ethylene (ET) and nitric oxide (NO) have been involved in the activation of both Fe-related and P-related genes. The common involvement of ET and NO suggests that they must act in conjunction with other specific signals, more closely related to each deficiency. Among the specific signals involved in the regulation of Fe- or P-related genes have been proposed Fe-peptides (or Fe ion itself) and microRNAs, like miR399 (P), moving through the phloem. These Fe- or P-related phloem signals could interact with ET/NO and confer specificity to the responses to each deficiency, avoiding the induction of the specific responses when ET/NO increase due to other nutrient deficiencies or stresses. Besides the specificity conferred by these signals, ET itself could confer specificity to the responses to Fe- or P-deficiency by acting through different signaling pathways in each case. Given the above considerations, there are preliminary results suggesting that ET could regulate different nutrient responses by acting both in conjunction with other signals and through different signaling pathways. Because of the close relationship among these two elements, a better knowledge of the physiological and molecular basis of their interaction is necessary to improve their nutrition and to avoid the problems associated with their misuse. As examples of this interaction, it is known that Fe chlorosis can be induced, under certain circumstances, by a P over- fertilization. On the other hand, Fe oxides can have a role in the immobilization of P in soils. Qualitative and quantitative assessment of the dynamic of known Fe- and P-related genes expression, selected ad hoc and involved in each of these deficiencies, would allow us to get a profound knowledge of the processes that regulate the responses to both deficiencies. The better knowledge of the regulation by ET of the responses to these deficiencies is necessary to properly understand the interactions between Fe and P. This will allow the obtention of more efficient varieties in the absorption of P and Fe, and the use of more rational management techniques for P and Fe fertilization. This will contribute to minimize the environmental impacts caused by the use of P and Fe fertilizers (Fe chelates) in agriculture and to adjust the costs for farmers, due to the high prices and/or scarcity of Fe and P fertilizers. This review aims to summarize the latest advances in the knowledge about Fe and P deficiency responses, analyzing the similarities and differences among them and considering the interactions among their main regulators, including some hormones (ethylene) and signaling substances (NO and GSNO) as well as other P- and Fe-related signals.     

Immune Checkpoint Inhibitors: A Promising Treatment Option for Metastatic Castration-Resistant Prostate Cancer?

Since 2010, several treatment options have been available for men with metastatic castration-resistant prostate cancer (mCRPC), including immunotherapeutic agents, although the clinical benefit of these agents remains inconclusive in unselected mCRPC patients. In recent years, however, immunotherapy has re-emerged as a promising therapeutic option to stimulate antitumor immunity, particularly with the use of immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 and CTLA-4 inhibitors. There is increasing evidence that ICIs may be especially beneficial in specific subgroups of patients with high PD-L1 tumor expression, high tumor mutational burden, or tumors with high microsatellite instability/mismatch repair deficiency. If we are to improve the efficacy of ICIs, it is crucial to have a better understanding of the mechanisms of resistance to ICIs and to identify predictive biomarkers to determine which patients are most likely to benefit. This review focuses on the current status of ICIs for the treatment of mCRPC (either as monotherapy or in combination with other drugs), mechanisms of resistance, potential predictive biomarkers, and future challenges in the management of mCRPC.     

Direct-Ink-Writing of Electroactive Polymers for Sensing and Energy Storage Applications

Considering the high levels of materials used in the fields of electronics and energy storage systems, it is increasingly necessary to take into consideration environmental impact. Thus, it is important to develop devices based on environmentally friendlier materials and/or processes, such as additive manufacturing techniques. In this work, poly(vinylidene fluoride) (PVDF) and poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) are prepared by direct-ink-writing (DIW) by varying solvent evaporation temperature and fill density percentage. Different morphologies for both polymers are obtained, including dense films and porous membranes, as well as different electroactive β-phase content, thermal and mechanical properties. The dielectric constant and piezoelectric d₃₃ coefficient for dense films reaches up to 16 at 1 kHz and 4 pC N⁻¹, respectively for PVDF-HFP with a fill density of 80 and a solvent evaporation temperature of 50 °C. Porous structures are developed for battery separator membranes in lithium-ion batteries, with a highest ionic conductivity value of 3.8 mS cm⁻¹ for the PVDF-HFP sample prepared with a fill density of 100 and a solvent evaporation temperature of 25 °C, the sample showing an excellent cycling performance. It is demonstrated that electroactive films and membranes can be prepared by direct-ink writing suitable for sensors/actuators and energy storage systems.     

A Methionine Chemical Shift Based Order Parameter Characterizing Global Protein Dynamics

Coupling of side chain dynamics over long distances is an important component of allostery. Methionine side chains show the largest intrinsic flexibility among methyl-containing residues but the actual degree of conformational averaging depends on the proximity and mobility of neighboring residues. The ¹³C NMR chemical shifts of the methyl groups of methionine residues located at long distances in the same protein show a similar scaling with respect to the values predicted from the static X-ray structure by quantum methods. This results in a good linear correlation between calculated and observed chemical shifts. The slope is protein dependent and ranges from zero for the highly flexible calmodulin to 0.7 for the much more rigid calcineurin catalytic domain. The linear correlation is indicative of a similar level of side-chain conformational averaging over long distances, and the slope of the correlation line can be interpreted as an order parameter of the global side-chain flexibility.     

Synthesis of some fumaric acid polyamides from active diester monomers

Summary The solution polycondensation of two active diesters, bis(2,4-dinitrophenyl) fumarate and 1,1-(fumaroyldioxy)bis(benzotriazole), with a series of alphatic and aromatic diamines in N-methyl pyrolidone at room temperature, was investigated. The polycondensation reactions yielded a series of fumaric acids polyamides. The polymers obtained from aliphatic diamines were soluble in trifluroacetic acid and exhibited well-defined melting points. The polymers obtained from aromatic diamines are infusible at temperatures below 300°C but were thermally stable and soluble in dimethylacetamide containing 4% LiC1.