Functional chromophores synthesized via multicomponent Reactions: A review on their use as cell-imaging probes.

This review aims to provide a comprehensive overview of recent advancements and applications of fluorescence imaging probes synthesized via MCRs (multicomponent reactions). These probes, also known as functional chromophores, belong to a currently investigated class of fluorophores that are presently being successfully applied in bioimaging experiments, especially in various living cell lineages. We describe some of the MCRs that have been employed in the synthesis of these probes and explore their applications in biological imaging, with an emphasis on cellular imaging. The review also discusses the challenges and future perspectives in the field, particularly considering the potential impact of MCR-based fluorescence imaging probes on advancing this field of research in the coming years. Considering that this area of research is relatively new and nearly a decade has passed since the first publication, this review also provides a historical perspective on this class of fluorophores, highlighting the pioneering works published between 2011 and 2016.

The role of light emitting diode in wound healing: A systematic review of experimental studies.

Wounds represent a growing global issue demanding increased attention. To expedite wound healing, technologies are under development, and light emitting diode (LED) devices of varying wavelengths are being explored for their stimulating influence on the healing process. This article presents a systematic literature review aiming to compile, organize, and analyze the impacts of LED devices on wound healing. This review is registered on the PROSPERO platform [CRD42023403870]. Two blinded authors conducted searches in the Pubmed, Web of Science, Scopus, Embase, and ScienceDirect databases. In vitro and in vivo experimental studies assessing LED utilization in the wound healing process were included. The search yielded 1010 studies, of which 27 were included in the review. It was identified that LED stimulates different healing pathways, promoting enhanced cell proliferation and migration, angiogenesis stimulation, increased collagen deposition, and modulation of the inflammatory response. Thus, it can be concluded that the LED stimulates cellular and molecular processes contingent on the utilized parameters. The effects depend on the standards used. Cell migration and proliferation were better influenced by green and red LED. The extracellular matrix components and angiogenesis were regulated by all wavelengths and the modulation of inflammation was mediated by green, red, and infrared LEDs.

COVID-19 Infection in Octagenarian Patients: Imaging Aspects and Clinical Correlations.

INTRODUCTION: Computed tomography (CT) of the chest, although not a screening test or diagnosis of infection with the new coronavirus, has a fundamental role in assessing the extent of lung involvement and complications such as pleural effusion. Considering the higher morbidity and mortality of elderly patients due to this infection, the objective of this study was to evaluate the imaging aspects and clinical correlations of an extreme age (≥80 years) with a confirmed diagnosis for COVID-19. METHODS: This was a retrospective and single-center cohort study. CT scans were categorized qualitatively and quantitatively. In the first case, 3 descriptors were used to describe CT findings: "compatible" (findings of greater specificity for COVID-19: opacities with attenuation in ground glass with peripheral and bilateral distribution, with rounded morphology, with or without consolidations, crazy-pavement aspect, inverted halo sign, or organizing pneumonia findings), "doubtful" (findings not specific or unusual for COVID-19: opacities with attenuation in ground glass with nonrounded morphology, central, diffuse, or unilateral distribution, with or without consolidation, lobar or segmental consolidation without ground-glass opacity, small centrilobular nodules with the appearance of "tree-in-bud," excavations, pleural effusion, and thickening of interlobular septa), and "negative" (absence of pneumonia signs). For the quantitative assessment, which referred to the extent of pulmonary involvement, a tomographic severity classification was used: grade 1 (lung involvement ≤25%), grade 2 (pulmonary involvement between 26 and 50%), and grade 3 (pulmonary involvement >50%). RESULTS: A total of 138 patients were evaluated, with an average age of 86.2 years (84 women and 34 men). The mean time interval between onset of symptoms and tomography was 5.63 days. The most prevalent comorbidity was systemic arterial hypertension (81.2%). Compatible, doubtful, and negative tests were 117 (84.7%), 20 (14.4%), and 1 (0.7%), respectively. As for compatible exams, the most common findings were opacities in peripheral ground glass and rounded morphology, followed by crazy paving. The prevalence of pleural effusion was 28.2% and consolidation was 63.7%, and none of these findings were influenced by the duration of symptoms (p = 0.08 and p = 0.2, respectively). The exams classified as grade 1, grade 2, and grade 3 were 57 (41.6%), 46 (33.6%), and 34 (24.8%), respectively. There were statistically significant associations between the classification of tomographic severity and outcomes such as invasive ventilation (p = 0.004), admission to the intensive care unit (p < 0.001), and death (p < 0.001). DISCUSSION/CONCLUSION: Our results show that patients ≥80 years old present tomographic manifestations similar to those described for the general population (ground-glass opacities and "crazy paving") and that the extent of lung involvement is associated with the need for intensive care, invasive ventilation, and death. Although the literature describes an association between the stage of the disease and the appearance of consolidations and pleural effusion, this correlation was not observed in our study, which may suggest that this age-group is more predisposed to the appearance of such findings, typically described in the more advanced stages of infection.

Automated Notification of Relevant Expected or Incidental Findings in Imaging Exams in a Verticalized Healthcare System.

To describe the implementation of a standardized code system for notification of relevant expected or incidental findings in imaging exams and use of an automated textual mining tool of radiological report narratives, created to facilitate directing patients to specific lines of care, reducing the waiting time for interventions, consultations, and minimizing delays to treatment. We report our 12-month initial experience with the process. A standardized code was attached to every radiology report when a relevant finding was observed. On a daily basis, the notifications was sent to a dedicated medical team to review the notified abnormality and decide a proper action. Between October 1, 2020, and September 30, 2021, 40,296 sectional examinations (CT and MR scans) were evaluated in 35,944 patients. The main findings reported were calcified plaques on the trunk of the left coronary artery or trunk like, pulmonary nodule/mass and suspected liver disease. Data of follow-up was available in 10,019 patients. The age ranged from 24 to 101 years (mean of 71.3 years) and 6,626 were female (66.1%). In 2,548 patients a complementary study or procedure was indicated, and 3,300 patients were referred to a specialist. Customized database searches looking for critical or relevant findings may facilitate patient referral to specific care lines, reduce the waiting time for interventions or consultations, and minimize delays to treatment.

Systematic analysis of 1298 RNA-Seq samples and construction of a comprehensive soybean (Glycine max) expression atlas.

Soybean (Glycine max [L.] Merr.) is a major crop in animal feed and human nutrition, mainly for its rich protein and oil contents. The remarkable rise in soybean transcriptome studies over the past 5 years generated an enormous amount of RNA-seq data, encompassing various tissues, developmental conditions and genotypes. In this study, we have collected data from 1298 publicly available soybean transcriptome samples, processed the raw sequencing reads and mapped them to the soybean reference genome in a systematic fashion. We found that 94% of the annotated genes (52 737/56 044) had detectable expression in at least one sample. Unsupervised clustering revealed three major groups, comprising samples from aerial, underground and seed/seed-related parts. We found 452 genes with uniform and constant expression levels, supporting their roles as housekeeping genes. On the other hand, 1349 genes showed heavily biased expression patterns towards particular tissues. A transcript-level analysis revealed that 95% (70 963 of 74 490) of the assembled transcripts have intron chains exactly matching those from known transcripts, whereas 3256 assembled transcripts represent potentially novel splicing isoforms. The dataset compiled here constitute a new resource for the community, which can be downloaded or accessed through a user-friendly web interface at http://venanciogroup.uenf.br/resources/. This comprehensive transcriptome atlas will likely accelerate research on soybean genetics and genomics.

EIF2α phosphorylation is regulated in intracellular amastigotes for the generation of infective Trypanosoma cruzi trypomastigote forms.

Trypanosomatids regulate gene expression mainly at the post-transcriptional level through processing, exporting and stabilising mRNA and control of translation. In most eukaryotes, protein synthesis is regulated by phosphorylation of eukaryotic initiation factor 2 (eIF2) at serine 51. Phosphorylation halts overall translation by decreasing availability of initiator tRNAmet to form translating ribosomes. In trypanosomatids, the N-terminus of eIF2α is extended with threonine 169 the homologous phosphorylated residue. Here, we evaluated whether eIF2α phosphorylation varies during the Trypanosoma cruzi life cycle, the etiological agent of Chagas' disease. Total levels of eIF2α are diminished in infective and non-replicative trypomastigotes compared with proliferative forms from the intestine of the insect vector or amastigotes from mammalian cells, consistent with decreased protein synthesis reported in infective forms. eIF2α phosphorylation increases in proliferative intracellular forms prior to differentiation into trypomastigotes. Parasites overexpressing eIF2αT169A or with an endogenous CRISPR/Cas9-generated eIF2αT169A mutation were created and analysis revealed alterations to the proteome, largely unrelated to the presence of µORF in epimastigotes. eIF2αT169A mutant parasites produced fewer trypomastigotes with lower infectivity than wild type, with increased levels of sialylated mucins and oligomannose glycoproteins, and decreased galactofuranose epitopes and the surface protease GP63 on the cell surface. We conclude that eIF2α expression and phosphorylation levels affect proteins relevant for intracellular progression of T. cruzi.

Synthetic enzyme-catalyzed multicomponent reaction for Isoxazol-5(4H)-one Syntheses, their properties and biological application; why should one study mechanisms?

In this work, we describe the application of a synthetic enzyme (synzyme) as the catalyst to promote the multicomponent synthesis of isoxazol-5(4H)-one derivatives. The catalytic system could be used up to 15 times without any notable loss of its activity. Some derivatives showed fluorescence and their photophysical data were evaluated. The mechanism of the reaction was, for the first time, investigated and, among the three reaction pathway possibilities, only one was operating under the developed conditions. ESI-MS(/MS) allowed for both the simultaneous monitoring of the multicomponent reaction (MCR) and the proposition of a kinetic model to explain the transformation. The kinetic model pointed firmly to only one reaction pathway and helped to discard the other two possibilities. The antimicrobial abilities of all synthesized derivatives against Gram-positive and Gram-negative strains were also evaluated. The abilities of functional chromophores (fluorescent compounds) as live cell-imaging probes were verified and one of the multicomponent adducts could stain early endosomes selectively in bioimaging experiments.

Exploring the complexity of soybean (Glycine max) transcriptional regulation using global gene co-expression networks.

MAIN CONCLUSION: We report a soybean gene co-expression network built with data from 1284 RNA-Seq experiments, which was used to identify important regulators, modules and to elucidate the fates of gene duplicates. Soybean (Glycine max (L.) Merr.) is one of the most important crops worldwide, constituting a major source of protein and edible oil. Gene co-expression networks (GCN) have been extensively used to study transcriptional regulation and evolution of genes and genomes. Here, we report a soybean GCN using 1284 publicly available RNA-Seq samples from 15 distinct tissues. We found modules that are differentially regulated in specific tissues, comprising processes such as photosynthesis, gluconeogenesis, lignin metabolism, and response to biotic stress. We identified transcription factors among intramodular hubs, which probably integrate different pathways and shape the transcriptional landscape in different conditions. The top hubs for each module tend to encode proteins with critical roles, such as succinate dehydrogenase and RNA polymerase subunits. Importantly, gene essentiality was strongly correlated with degree centrality and essential hubs were enriched in genes involved in nucleic acids metabolism and regulation of cell replication. Using a guilt-by-association approach, we predicted functions for 93 of 106 hubs without functional description in soybean. Most of the duplicated genes had different transcriptional profiles, supporting their functional divergence, although paralogs originating from whole-genome duplications (WGD) are more often preserved in the same module than those from other mechanisms. Together, our results highlight the importance of GCN analysis in unraveling key functional aspects of the soybean genome, in particular those associated with hub genes and WGD events.

Chromatin Proteomics Reveals Variable Histone Modifications during the Life Cycle of Trypanosoma cruzi.

Histones are well-conserved proteins that form the basic structure of chromatin in eukaryotes and undergo several post-translational modifications, which are important for the control of transcription, replication, DNA damage repair, and chromosome condensation. In early branched organisms, histones are less conserved and appear to contain alternative sites for modifications, which could reveal evolutionary unique functions of histone modifications in gene expression and other chromatin-based processes. Here, by using high-resolution mass spectrometry, we identified and quantified histone post-translational modifications in two life cycle stages of Trypanosoma cruzi, the protozoan parasite that causes Chagas disease. We detected 44 new modifications, namely: 18 acetylations, seven monomethylations, seven dimethylations, seven trimethylations, and four phosphorylations. We found that replicative (epimastigote stage) contains more histone modifications than nonreplicative and infective parasites (trypomastigote stage). Acetylations of lysines at the C-terminus of histone H2A and methylations of lysine 23 of histone H3 were found to be enriched in trypomastigotes. In contrast, phosphorylation in serine 23 of H2B and methylations of lysine 76 of histone H3 predominates in proliferative states. The presence of one or two methylations in the lysine 76 was found in cells undergoing mitosis and cytokinesis, typical of proliferating parasites. Our findings provide new insights into the role of histone modifications related to the control of gene expression and cell-cycle regulation in an early divergent organism.

Recruitment of galectin-3 during cell invasion and intracellular trafficking of Trypanosoma cruzi extracellular amastigotes.

The invasion of host cells by the intracellular protozoan Trypanosoma cruzi requires interactions with host cell molecules, and the replication of the parasite requires escape from a parasitophorous vacuole into the host cell cytosol. Galectin-3, a member of ß-galactosidase-binding lectin family, has numerous extracellular and intracellular functions. In this study, we investigated the role of galectin-3 during the invasion and intracellular trafficking of T. cruzi extracellular amastigotes (EAs). Endogenous galectin-3 from mouse peritoneal macrophages accumulated around the pathogen during cell invasion by EAs. In addition, galectin-3 accumulated around parasites after their escape from the parasitophorous vacuole. Thus, galectin-3 behaved as a novel marker of phagolysosome lysis during the infection of host cells by T. cruzi.

Improving liveweight gain of lambs infected by multidrug-resistant nematodes using a FECRT-based schedule of treatments.

The aim of this study was to compare the liveweight gain of lambs, infected by multidrug-resistant nematodes, treated by conventional schemes of helminth control or using a schedule based on fecal egg count reduction test (FECRT). The flock was selected after a FECRT (experiment 1) which revealed a parasite population resistant to benzimidazoles, imidazothiazoles, macrocyclic lactones (ivermectin), salicylanilides, nitrophenols, and organophosphates. Despite the parasite resistance to ivermectin (an avermectin), the moxidectin (a milbemycin) was effective against the gastrointestinal nematodes (PR > 90%). In experiment 2, 48 suckling lambs were distributed in four randomized blocks (G1, G2, G3, and G4) by previous body weighings. G1 was kept as untreated control; G2 was treated following a FECRT-based schedule with drugs chosen based on fecal analysis (first drench with moxidectin, second drench with a combination of moxidectin and levamisole, and third drench with praziquantel, an anti-cestode drug); G3 and G4 received three drenches with ivermectin or disophenol, respectively. Body weighings and fecal analysis of these lambs were performed every 2 weeks over a 98-day period. An effective control of gastrointestinal nematodes was obtained with two nematicidal drenches following the FECRT-based schedule of treatments. On the other hand, eggs per gram of feces (EPG) counts were no different among untreated control, G3, and G4. Lambs treated using the FECRT-based schedule had the greatest liveweight gain among the groups tested. Additionally, liveweight gain was no different among the groups G3, G4, and G1. The FECRT-based schedule of anthelmintic treatments was beneficial regarding productivity and sustainability of helminth control in lambs infected by multidrug-resistant nematodes.

Seasonal variation of the chemical composition and antimicrobial and cytotoxic activities of the essential oils from Inga laurina (Sw.) Willd.

The seasonal chemical composition of essential oils from Inga laurina was determined by GC/MS. In the stem bark's essential oil extracted during the dry season, the presence of terpenoids (30.05%) stood out, and phytol (9.76%) was the major compound identified. For the stem bark oil obtained during the rainy season, in addition to terpenoids (26.63%), a large amount of fatty acids (46.84%) were identified, in particular palmitic acid (25.40%). Regarding the leaves' essential oil obtained in the dry season, esters (42.35%) were the main components. The main ester present was (Z)-hex-3-enyl benzoate (10.15%) and the major compound of this oil was (Z)-hex-3-en-1-ol (14.23%). Terpenoids (33.84%), long-chain alkanes (27.04%) and fatty acids (21.72%) were the main components of the essential oil from leaves in the rainy season. Phytol (33.21%), nonacosane (21.95%) and palmitic acid (15.20%) were the major compounds identified. The antimicrobial activity against aerobic and anaerobic oral bacteria was evaluated by the microdilution broth method and cytotoxic activity was carried out with Vero cells. The essential oils from the rainy season showed a better inhibition of the bacterial growth with Minimal Inhibitory Concentrations (MIC) values of 25 or 50 µg·mL⁻¹ for aerobic bacteria, and high selectivity against bacteria was observed. The large amount of fatty acids in rainy season oils may be related to the better inhibitory effects observed.

Astaxanthin induces autophagy and apoptosis in murine melanoma B16F10-Nex2 cells and exhibits antitumor activity in vivo.

Countless efforts have been made to prevent and suppress the formation and spread of melanoma. Natural astaxanthin (AST; extracted from the alga Haematococcus pluvialis) showed an antitumor effect on various cancer cell lines due to its interaction with the cell membrane. This study aimed to characterize the antitumor effect of AST against B16F10-Nex2 murine melanoma cells using cell viability assay and evaluate its mechanism of action using electron microscopy, western blotting analysis, terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay, and mitochondrial membrane potential determination. Astaxanthin exhibited a significant cytotoxic effect in murine melanoma cells with features of apoptosis and autophagy. Astaxanthin also decreased cell migration and invasion in vitro assays at subtoxic concentrations. In addition, assays were conducted in metastatic cancer models in mice where AST significantly decreased the development of pulmonary nodules. In conclusion, AST has cytotoxic effect in melanoma cells and inhibits cell migration and invasion, indicating a promising use in cancer treatment.

A facile one step route that introduces functionality to polymer powders for laser sintering.

Laser Sintering (LS) is a type of Additive Manufacturing (AM) exploiting laser processing of polymeric particles to produce 3D objects. Because of its ease of processability and thermo-physical properties, polyamide-12 (PA-12) represents ~95% of the polymeric materials used in LS. This constrains the functionality of the items produced, including limited available colours. Moreover, PA-12 objects tend to biofoul in wet environments. Therefore, a key challenge is to develop an inexpensive route to introduce desirable functionality to PA-12. We report a facile, clean, and scalable approach to modification of PA-12, exploiting supercritical carbon dioxide (scCO2) and free radical polymerizations to yield functionalised PA-12 materials. These can be easily printed using commercial apparatus. We demonstrate the potential by creating coloured PA-12 materials and show that the same approach can be utilized to create anti-biofouling objects. Our approach to functionalise materials could open significant new applications for AM.

Chemical composition, cytotoxic and antimicrobial activity of essential oils from Cassia bakeriana Craib. against aerobic and anaerobic oral pathogens.

The chemical composition of the essential oils from leaves, bark and wood of Cassia bakeriana Craib. was determined by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). Alcohols, aldehydes and fatty acids were the major components in leaf and bark oil, while wood essential oil was rich in fatty acids. Terpenes such as linalool, (E)-nerolidol and phytol were present in low concentrations. The antimicrobial activity against aerobic and anaerobic oral bacteria was evaluated using the microdilution method, as was the cell viability test carried out with Vero cells. The oils from leaves and bark showed high antimicrobial activity, with minimum inhibitory concentrations between 62.5 and 125 µg·mL⁻¹ for most of the tested bacteria, including Streptococcus mutans, the main etiological agent of dental caries. Leaves oil displayed the lowest cytotoxic effect (EC50 of 153 µg·mL⁻¹), while wood oil exhibited the highest toxicity to Vero cells. C. bakeriana oils are thus a source of biologically active compounds against aerobic and anaerobic oral microorganisms. This study is the first report on the chemical composition, antimicrobial activity and cytotoxicity of C. bakeriana.

Improvement of enzymatic saccharification by simultaneous pulping of sugarcane bagasse and washing of its cellulose fibers in a batch reactor.

A modification of the conventional batch organosolv process is proposed in a way where the solid biomass remains inside a basket, physically separated from the liquid phase, with the vapor promoting the fractionation of the biomass and the extracted compounds and fragments being washed down to the liquid phase. The modified organosolv process applied to sugarcane bagasse (SB-M) delivers a rich cellulosic solid phase that after enzymatic hydrolysis leads to a hydrolyzed with approximately 100 g L-1 of glucose. At the same enzymatic hydrolysis conditions, the conventional organosolv process (SB-C) delivers a hydrolyzed with 80 g L-1 of glucose, while the autohydrolysis process (SB-A) leads to 55 g L-1 of glucose. These different results are related to the cellulose content: SB-M (70%), SB-C (57%), e SB-A (44%), as well the reduced lignin content in the SB-M. The novelty of this study is the confirmation that it is possible to degrade lignin from sugarcane bagasse and simultaneously remove its fragments from the cellulose fibers in a batch reactor containing an internal basket. This study describes a simple and rapid protocol for the isolation of the main components of lignocellulosic biomass (cellulose, hemicellulose, and lignin), which may lead to the study of new catalysts for the chemical transformation of these components separately or simultaneously to the step of pretreatment.

Influence of Reduction with NaBH4 and HCl in Obtaining Amino Derivatives of Cashew Gum and Cytotoxic Profile.

Tree-exuded gums are natural polymers that represent an abundant raw material in the food and pharmaceutical industries. The cashew gum can be obtained by exudation of trees of the genus Anacardium, a native species of the Brazilian northeast; its polymer consists of monosaccharide units propitious to the action of chemical reactions that tend to improve their intrinsic characteristics among them, as the degree of hydro-solubility. The objective of this work was to modify the exudate gum of Anacardium occidentale (cashew gum (CG)) through an amine reaction. The modification was confirmed by Nuclear Magnetic Resonance (1H NMR), infrared spectroscopy (FTIR), gel permeation chromatography (GPC), zeta potential, and thermogravimetric analysis (TG). In addition, the chemical modification altered the molar mass and surface charge of the CG, and the amino group binding to the CG polymers was confirmed by FTIR spectra. In addition, cytotoxicity tests were performed where cell viability was estimated by an MTT assay on RAW 264.7 macrophages. Through these tests, it was found that the amine caused an increase in the thermal stability of the amino compounds and did not present cytotoxic potential at concentrations below 50.0 mg/L.

Evaluation of different strains of Saccharomyces cerevisiae for ethanol production from high-amylopectin BRS AG rice (Oryza sativa L.).

Ethanol is the main biofuel produced by fermentation route and the search for new feedstocks to produce fuel ethanol is still a great challenge. This work aims to compare the ethanol production from a new irrigated rice cultivar BRS AG to the conventional cultivar BRS PAMPA applied in Brazil. Six different commercial strains of Saccharomyces cerevisiae (BG-1, CAT-1, FT-858, JP-1, PE-2, and SA-1) were applied in fermentation reactions. Fermentations performed with BRS PAMPA rice revealed that the highest yields were achieved with strain SA-1, corresponding to 93.0% of the theoretical maximum and final ethanol concentration of 58.92 g L-1, and with CAT-1, a yield of 92.7% and final ethanol concentration of 58.93 g L-1. For the fermentations with BRS AG rice, the highest yields were obtained with strain FT-858, exhibiting a 89.6% yield and final ethanol concentration of 62.45 g L-1, and with CAT-1, 87.9% yield and final ethanol concentration of 61.25 g L-1 were achieved. The most appropriate microorganism for ethanol production using BRS PAMPA rice and BRS AG rice was CAT-1. Comparatively, the ethanol yield and productivity using BRS AG were higher than those observed for BRS PAMPA for all strains, except for PE-2 and SA-1 that led to very similar results. The experimental results showed that the giant rice BRS AG is an excellent feedstock for fuel ethanol production in lowland fields.

Comparative hydrodynamic characterisation of two hydroxylated polymers based on α-pinene- or oleic acid-derived monomers for potential use as archaeological consolidants.

The Oseberg Viking ship burial is one of the most extensive collections of Viking wooden artefacts ever excavated in Norway. In the early twentieth century, many of these artefacts were treated with alum in order to preserve them, inadvertently leading to their current degraded state. It is therefore crucial to develop new bioinspired polymers which could be used to conserve these artefacts and prevent further disintegration. Two hydroxylated polymers were synthesised (TPA6 and TPA7), using α-pinene- and oleic acid-derived monomers functionalised with an acrylate moiety. Characterisation using biomolecular hydrodynamics (analytical ultracentrifugation and high precision viscometry) has shown that these polymers have properties which would potentially make them good wood consolidants. Conformation analyses with the viscosity increment (ν) universal hydrodynamic parameter and ELLIPS1 software showed that both polymers had extended conformations, facilitating in situ networking when applied to wood. SEDFIT-MSTAR analyses of sedimentation equilibrium data indicates a weight average molar mass Mw of (3.9 ± 0.8) kDa and (4.2 ± 0.2) kDa for TPA6 and TPA7 respectively. Analyses with SEDFIT (sedimentation velocity) and MultiSig however revealed that TPA7 had a much greater homogeneity and a lower proportion of aggregation. These studies suggest that both these polymers-particularly TPA7-have characteristics suitable for wood consolidation, such as an optimal molar mass, conformation and a hydroxylated nature, making them interesting leads for further research.

PLP2-derived peptide Rb4 triggers PARP-1-mediated necrotic death in murine melanoma cells.

Malignant melanoma is the main cause of death in patients with skin cancer. Overexpression of Proteolipid protein 2 (PLP2) increased tumor metastasis and the knockdown of PLP2 inhibited the growth and metastasis of melanoma cells. In the present work, we studied the antitumor activity of peptide Rb4 derived from protein PLP2. In vitro, Rb4 induced F-actin polymerization, prevented F-actin depolymerization and increased the ER-derived cytosolic calcium. Such effects were associated with necrosis of murine melanoma B16F10-Nex2 cells and with inhibition of the viability of human cancer cell lines. Loss of plasma membrane integrity, dilation of mitochondria, cytoplasm vacuolation and absence of chromatin condensation characterized tumor cell necrosis. Cleavage of PARP-1 and inhibition of RIP1 expression were also observed. In vivo, peptide Rb4 reduced the lung metastasis of tumor cells and delayed the subcutaneous melanoma growth in a syngeneic model. Rb4 induced the expression of two DAMPs molecules, HMGB1 and calreticulin, in B16F10-Nex2. Our results suggest that peptide Rb4 acts directly on tumor cells inducing the expression of DAMPs, which trigger the immunoprotective effect in vivo against melanoma cells. We suggest that peptide Rb4 is a promising compound to be developed as an anticancer drug.