COVID-19 and Lung Mast Cells: The Kallikrein–Kinin Activation Pathway

Mast cells (MCs) have relevant participation in inflammatory and vascular hyperpermeability events, responsible for the action of the kallikrein–kinin system (KKS), that affect patients inflicted by the severe form of COVID-19. Given a higher number of activated MCs present in COVID-19 patients and their association with vascular hyperpermeability events, we investigated the factors that lead to the activation and degranulation of these cells and their harmful effects on the alveolar septum environment provided by the action of its mediators. Therefore, the pyroptotic processes throughout caspase-1 (CASP-1) and alarmin interleukin-33 (IL-33) secretion were investigated, along with the immunoexpression of angiotensin-converting enzyme 2 (ACE2), bradykinin receptor B1 (B1R) and bradykinin receptor B2 (B2R) on post-mortem lung samples from 24 patients affected by COVID-19. The results were compared to 10 patients affected by H1N1pdm09 and 11 control patients. As a result of the inflammatory processes induced by SARS-CoV-2, the activation by immunoglobulin E (IgE) and degranulation of tryptase, as well as Toluidine Blue metachromatic (TB)-stained MCs of the interstitial and perivascular regions of the same groups were also counted. An increased immunoexpression of the tissue biomarkers CASP-1, IL-33, ACE2, B1R and B2R was observed in the alveolar septum of the COVID-19 patients, associated with a higher density of IgE⁺ MCs, tryptase⁺ MCs and TB-stained MCs, in addition to the presence of intra-alveolar edema. These findings suggest the direct correlation of MCs with vascular hyperpermeability, edema and diffuse alveolar damage (DAD) events that affect patients with a severe form of this disease. The role of KKS activation in events involving the exacerbated increase in vascular permeability and its direct link with the conditions that precede intra-alveolar edema, and the consequent DAD, is evidenced. Therapy with drugs that inhibit the activation/degranulation of MCs can prevent the worsening of the prognosis and provide a better outcome for the patient.     

Composites based on high-density polyethylene,polylactide and calcium carbonate: effect of calcium carbonate nanoparticles as co-compatibilizers

Polymer Bulletin - Investigating the compatibility mechanism of hybrid composites based on two polymers and one mineral nanofiller is a challenge that needs to be better understood. This study...     

Solid Tumors and Kinase Inhibition: Management and Therapy Efficacy Evolution

The increasing numbers of cancer cases worldwide and the exceedingly high mortality rates of some tumor subtypes raise the question about if the current protocols for cancer management are effective and what has been done to improve upon oncologic patients’ prognoses. The traditional chemo-immunotherapy options for cancer treatment focus on the use of cytotoxic agents that are able to overcome neoplastic clones’ survival mechanisms and induce apoptosis, as well as on the ability to capacitate the host’s immune system to hinder the continuous growth of malignant cells. The need to avert the highly toxic profiles of conventional chemo-immunotherapy and to overcome the emerging cases of tumor multidrug resistance has fueled a growing interest in the field of precision medicine and targeted molecular therapies in the last couple of decades, although relatively new alternatives in oncologic practices, the increased specificity, and the positive clinical outcomes achieved through targeted molecular therapies have already consolidated them as promising prospects for the future of cancer management. In recent years, the development and application of targeted drugs as tyrosine kinase inhibitors have enabled cancer treatment to enter the era of specificity. In addition, the combined use of targeted therapy, immunotherapy, and traditional chemotherapy has innovated the standard treatment for many malignancies, bringing new light to patients with recurrent tumors. This article comprises a series of clinical trials that, in the past 5 years, utilized kinase inhibitors (KIs) as a monotherapy or in combination with other cytotoxic agents to treat patients afflicted with solid tumors. The results, with varying degrees of efficacy, are reported.     

Methylmercury Causes Neurodegeneration and Downregulation of Myelin Basic Protein in the Spinal Cord of Offspring Rats after Maternal Exposure

Methylmercury (MeHg) is one of the most dangerous toxic pollutants spread throughout the earth. Chronic MeHg intoxication by contaminated food ingestion is the most common threat to human health, including impairment to the developing fetus. The present study aims at investigating the effects of maternal exposure to MeHg during gestation and lactation on the spinal cord of offspring. Pregnant rats received oral doses of MeHg (40 μg/kg/day) over a period of 42 days (21 gestation and 21 lactation). Control animals received the vehicle only. Total mercury concentration was measured in blood samples from offspring collected at the 41st postnatal day. Counting of motor neurons and immunoreactivity for myelin basic protein (MBP) were assessed in the spinal cords in both control and MeHg-intoxicated animals. Our results showed that MeHg promoted an increase in blood Hg levels. In addition, it caused a reduction in the number of spinal cord motor neurons as well as decreased MBP immunoreactivity in the cervical, thoracic and lumbar segments. Our present findings suggest that MeHg intoxication during rat pregnancy and lactation is associated with a pattern of motor neuron degeneration and downregulation of myelin basic protein in different segments of a developing spinal cord. Further studies are needed to establish the effect of MeHg intoxication in both young and adult rats.     

Leptosphaeria maculans-Brassica napus Battle: A Comparison of Incompatible vs. Compatible Interactions Using Dual RNASeq

Leptosphaeria maculans causes blackleg disease, which is one of the most destructive diseases of canola (Brassica napus L.). Due to the erosion of the current resistance in B. napus, it is pivotal to introduce new resistant genotypes to the growers. This study evaluated the potential of Rlm7 gene as resistance to its corresponding avirulence AvrLm7 gene is abundant. The Rlm7 line was inoculated with L. maculans isolate with AvrLm7; UMAvr7; and the CRISPR/Cas9 knockout AvrLm7 mutant, umavr7, of the same isolate to cause incompatible and compatible interactions, respectively. Dual RNA-seq showed differential gene expressions in both interactions. High expressions of virulence-related pathogen genes-CAZymes, merops, and effector proteins after 7-dpi in compatible interactions but not in incompatible interaction—confirmed that the pathogen was actively virulent only in compatible interactions. Salicyclic and jasmonic acid biosynthesis and signaling-related genes, defense-related PR1 gene (GSBRNA2T00150001001), and GSBRNA2T00068522001 in the NLR gene family were upregulated starting as early as 1- and 3-dpi in the incompatible interaction and the high upregulation of those genes after 7-dpi in compatible interactions confirmed the early recognition of the pathogen by the host and control it by early activation of host defense mechanisms in the incompatible interaction.     

Bioactive compounds present in the Mediterranean sofrito

Sofrito is a key component of the Mediterranean diet, a diet that is strongly associated with a reduced risk of cardiovascular events. In this study, different Mediterranean sofritos were analysed for their content of polyphenols and carotenoids after a suitable work-up extraction procedure using liquid chromatography/electrospray ionisation-linear ion trap quadrupole-Orbitrap-mass spectrometry (LC/ESI-LTQ-Orbitrap-MS) and liquid chromatography/electrospray ionisation tandem triple quadrupole mass spectrometry (LC/ESI-MS-MS). In this way, 40 polyphenols (simple phenolic and hydroxycinnamoylquinic acids, and flavone, flavonol and dihydrochalcone derivatives) were identified with very good mass accuracy (<2 mDa), and confirmed by accurate mass measurements in MS and MS² modes. The high-resolution MS analyses revealed the presence of polyphenols never previously reported in Mediterranean sofrito. The quantification levels of phenolic and carotenoid compounds led to the distinction of features among different Mediterranean sofritos according to the type of vegetables (garlic and onions) or olive oil added for their production.     

Effect of preheating on potato texture

Preheating potatoes at 50 to 80°C has a firming effect on the cooked potato tissue. This effect is particularly pronounced at a preheating temperature of 60 to 70°C followed by cooling. Several theories have been presented in the literature to explain this firming effect: retrogradation of starch, leaching of amylose, stabilization of the middle lamellae and cell walls by the activation of the pectin methylesterase (PME) enzyme, and by the release of calcium from gelatinized starch and the formation of calcium bridges between pectin molecules. Most probably, none of these theories alone can explain the phenomenon and more than one mechanism seems to be involved. Some of these mechanisms seem to be interdependent. As an example, calcium could be considered as a link all the way through release after starch gelatinization to cross‐linking pectin substances in the cell wall and the middle lamellae, which has been demethylated by the PME enzyme. More research and “clear cut” experiments are needed in order to elucidate the role of each mechanism, especially which of them is the main contributor to the process of firming. Most probably, the calcium‐pectin‐PME mechanism plays a secondary role, that is, it only retards the collapse of the tissue structure that would otherwise occur during the final heating without preheating, and it is not the main factor of firmness.     

Biotransformation of Waste Bile Acids: A New Possible Sustainable Approach to Anti-Fungal Molecules for Crop Plant Bioprotection?

Phytopathogenic fungi are among the main causes of productivity losses in agriculture. To date, synthetic chemical pesticides, such as hydroxyanilides, anilinopyrimidines and azole derivatives, represent the main treatment tools for crop plant defence. However, the large and uncontrolled use of these substances has evidenced several side effects, namely the resistance to treatments, environmental damage and human health risks. The general trend is to replace chemicals with natural molecules in order to reduce these side effects. Moreover, the valorisation of agri-food industry by-products through biotransformation processes represents a sustainable alternative to chemical synthesis in several sectors. This research is aimed at comparing the anti-phytopathogenic activity of waste bovine and porcine bile with secosteroids obtained by biotransformation of bile acids with Rhodococcus strains. The ultimate goal is to apply these natural products on food crops affected by phytopathogenic fungi.     

Effects of mixing protocol on morphology and properties of PA6/ABS blends compatibilized with MMA‐MA

The effect of different mixing protocols in the preparation of PA6/ABS/MMA‐MA (57.5/37.5/5 wt %) blends on their morphological, rheological, thermal, thermomechanical, and mechanical behavior were studied. Despite the second‐phase size reduction due to copolymer incorporation, mixing sequence seems to play an important role in the properties of the blends. When PA6 is blended with the pre‐blended ABS/MMA‐MA system, compatibilizer is preferentially located in ABS phase and a co‐continuous structure is formed. The co‐continuity is believed to be responsible for the enhancements in toughness, but excessive presence of MMA‐MA in ABS phase seems to hamper thermomechanical properties. On the other hand, when ABS is blended with the PA6/MMA‐MA system previously prepared, compatibilizer is preferentially located in PA6 phase and a particle‐in‐matrix morphology is observed. The absence of excessive amount of MMA‐MA in ABS phase avoids the negative effect on thermomechanical resistance, however enhancements in toughness are not so pronounced. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43612.     

The effect of fibre concentration on the α to β-phase transformation, degree of crystallinity and electrical properties of vapour grown carbon nanofibre/poly(vinylidene fluoride) composites

Vapour growth carbon nanofibres/poly(vinilidene fluoride) - VGCNF/PVDF - composites prepared by solution casting were studied. The spherulitic crystallisation morphology of the pure polymer is maintained for the composites. Mechanical stretching of the composite films induces the α to β-phase transformation within the polymer matrix. This phase transition is accompanied by the destruction of the spherulitic microstructure in favour of a microfibrillar one. The incorporation of the VGCNF in the PVDF matrix increases the degree of crystallinity of the polymer composites for concentrations lower than ∼1%, remaining stable for higher VGCNF concentrations. With respect to the electrical properties, the stretching associated to the phase transformation induces a change in the conduction mechanism: the α-phase composite demonstrates a percolative behaviour on the measured conductivity whereas the β-phase demonstrates typical ionic conduction behaviour. Dielectric measurements in conjunction with the the two exponent percolation phenomenological equation demonstrates that in the β-phase an effective reduction in the ratio VGCNF length/domain length could induce the observed percolation behaviour.