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BACKGROUND: Sickle cell disease (SCD) affects approximately 100,000 people in the United States and millions worldwide, with the highest prevalence of 70% of SCD being found in individuals of African ethnicity. Delayed hemolytic, alloimmunization, and anamnestic transfusion reactions in multiple transfusion patients need to be investigated and managed to avoid a worsening of the patient's clinical status. OBJECTIVE: This paper aims to investigate delayed transfusion reactions in SCD patients who were polytransfused in the Brazilian Amazon. MATERIAL AND METHODS: The clinical and laboratory indicators of SCD patients with more than four transfusions were investigated. The patients were treated at the Fundação Hospitalar de Hematologia e Hemoterapia do Estado do Amazonas, Brazil. RESULTS: A total of 44 polytransfused patients with SCD were followed. Regarding Rh phenotype, it was possible to observe a frequency of 26.6% (12) patients with the RZRZ (DCE/DCE) phenotype, in addition to 4.5% (two) patients with RH and RHCE variants. It was also possible to observe 20.5% (nine) patients with an alloimmunization reaction, who presented the following alloantibodies: anti-RhD, anti-E, anti-K, anti-Jkb, anti-N, anti-S, and anti-Dia, two of which are unidentified. Of these, four (44.4%) patients also presented autoantibodies, anti-e, and three unidentified antibodies, and four (44.4%) patients presented an anamnestic reaction, with anti-RhD, K, and Jkb antibodies. Of the 44 patients monitored, 54.4% (24) had clinical and laboratory indicators of a delayed hemolytic reaction. CONCLUSION: Delayed transfusion reactions, often neglected, occur frequently. Therefore, transfusions need to be monitored for at least 28 days, with medical investigation of clinical and laboratory indicators to make greater use of this therapeutic resource.
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Wounds or chronic injuries are associated with high medical costs so, develop healing-oriented drugs is a challenge for modern medicine. The identification of new therapeutic alternatives focuses on the use of natural products. Therefore, the main goal of this study was to evaluate the healing potential and anti-inflammatory mechanism of action of extracts and the main compounds derived from Myrciaria plinioides D. Legrand leaves. The antimicrobial activity of leaf extracts was analyzed. Cell viability, cytotoxicity and genotoxicity of plant extracts and compounds were also assessed. Release of pro- and anti-inflammatory cytokines and TGF-ß by ELISA, and protein expression was determined by Western Blot. The cell migration and cell proliferation of ethanol and aqueous leaf extracts and p-coumaric acid, quercetin and caffeic acid compounds were also evaluated. The aqueous extract exhibited antibacterial activity and, after determining the safety concentrations in three assays, we showed that this extract induced p38-α MAPK phosphorylation and the same extract and the p-coumaric acid decreased COX-2 and caspase-3, -8 expression, as well as reduced the TNF-α release and stimulated the IL-10 in RAW 264.7 cells. In L929 cells, the extract and p-coumaric acid induced TGF-ß release, besides increasing the process of cell migration and proliferation. These results suggested that the healing properties of Myrciaria plinioides aqueous extract can be associated to the presence of phenolic compounds, especially p-coumaric acid, and/or glycosylated metabolites.
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Glyphosate, the world's most widely used herbicide, has a low toxicity rating despite substantial evidence of adverse health effects. Furthermore, glyphosate-based formulations (GBFs) contain several other chemicals, some of which are known to be harmful. Additionally, chronic, and acute exposure to GBFs among rural workers may lead to health impairments, such as neurodegenerative diseases and cancer. P53 is known as a tumor suppressor protein, acting as a key regulator of the cellular response to stress and DNA damage. Therefore, mutations in the TP53 gene, which encodes p53, are common genetic alterations found in various types of cancer. Therefore, this study aimed to evaluate the cytotoxicity and genotoxicity of GBF in two glioblastoma cell lines: U87MG (TP53-proficient) and U251MG (TP53-mutant). Additionally, the study aimed to identify the main proteins involved in the response to GBF exposure using Systems Biology in a network containing p53 and another network without p53. The MTT assay was used to study the toxicity of GBF in the cell lines, the clonogenic assay was used to investigate cell survival, and the Comet Assay was used for genotoxicity evaluation. For data analysis, bioinformatics tools such as String 12.0 and Stitch 5.0 were applied, serving as a basis for designing binary networks in the Cytoscape 3.10.1 program. From the in vitro test analyses, it was observed a decrease in cell viability at doses starting from 10â¯ppm. Comet Assay at concentrations of 10â¯ppm and 30â¯ppm for the U251MG and U87MG cell lines, respectively observed DNA damage. The network generated with systems biology showed that the presence of p53 is important for the regulation of biological processes involved in genetic stability and neurotoxicity, processes that did not appear in the TP53-mutant network.
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In this study, Eugenia calycina and Eugenia stigmatosa, native Brazilian berries, were explored regarding their proximal composition, bioactive compounds, and antioxidant activities. The edible parts of both fruits presented a low content of lipids, proteins, and carbohydrates, resulting in a low caloric value (<70 kcal/100 g fw). E. stigmatosa fruit showed a high total fiber content (3.26 g/100 g fw), qualifying it as a source of dietary fiber. The sugar profile was mainly monosaccharides (glucose, fructose, and rhamnose). Significant contents of total phenolics and flavonoids, monomeric anthocyanins and, condensed tannins, were observed in both fruits. E. calycina contains a high level of anthocyanins, primarily cyanidin-3-glucoside (242.97 µg/g). Other phenolic compounds were also found, the main ones being rutin and ellagic acid. In contrast, E. stigmatosa is mainly composed of rutin and gallic acid. Furthermore, these fruits showed expressive antioxidant activity, evidenced by ORAC, FRAP, and ABTS. These Eugenia fruits are promising sources of bioactive compounds and have a low caloric and high dietary fiber content, making them interesting options for inclusion in a balanced diet, contributing to the promotion of health and the valorization and conservation of Brazilian biodiversity.
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Coal is a mixture of several chemicals, many of which have mutagenic and carcinogenic effects and are a key contributor to the global burden of mortality and disease. Previous studies suggest that coal is related to telomeric shortening in individuals occupationally exposed, however little is known about the effects of mining and burning coal on the telomeres of individuals living nearby. Therefore, the primary objective of this investigation was to assess the impact of proximity to coal power plants and coal mines on the genomic instability of individuals environmentally exposed, while also exploring potential associations with individual characteristics, oxidative stress, inflammatory responses, and the presence of inorganic elements. This study involved 80 men participants from three cities around a thermoelectric power plant and one city unexposed to coal and byproducts. DNA was extracted from peripheral blood samples obtained from each participant, and the telomeres length (TL) was assessed using quantitative real-time polymerase chain reaction (qPCR) methodology. No significant difference was observed between exposed individuals (6227 ± 2884â¯bp) when compared to the unexposed group (5638 ± 2452â¯bp). Nevertheless, TL decrease was associated with age and risk for cardiovascular disease; and longer TL was found to be linked with increased concentrations of silicon and phosphorus in blood samples. No correlations were observed between TL with comet assay (visual score), micronucleus test, oxidative stress, and inflammatory results. Additional research is required to ascertain the potential correlation between these changes and the onset of diseases and premature mortality.
Subject(s)
Coal , DNA Damage , Environmental Exposure , Oxidative Stress , Power Plants , Telomere , Humans , Male , Coal/adverse effects , Middle Aged , Adult , Environmental Exposure/adverse effects , Telomere/drug effects , Telomere/genetics , Oxidative Stress/drug effects , Telomere Shortening/drug effects , Comet Assay , Micronucleus Tests , Coal Mining , Occupational Exposure/adverse effects , Aged , Telomere Homeostasis/drug effectsABSTRACT
The Gastroenterology Immunology Neuroscience (GIN) Discovery Program represents a new model for research that overcomes the limitations imposed by traditional "research silos" in science. By uniting these three fields, the GIN Program aims to enhance the understanding and treatment of chronic conditions through a system-wide perspective focusing on the gut-immune-brain axis. Key initiatives include monthly interdisciplinary seminars, an annual symposium, and GINnovate, a commercialization and entrepreneurship event. Additionally, the program offers a seed grant competition for early and mid-career researchers, promoting advancements in gut-immune-brain axis research through the power of collaboration. The GIN Program in a short period of time has facilitated the formation of a vibrant community, captivating attention from both national and international institutions. This effort to break down barriers in research aims to inspire similar models that prioritize open communication, mutual respect and a commitment to impactful science.
ABSTRACT
In this paper, we quantify weak protein-protein interactions in solution using cross-interaction chromatography (CIC) and surface plasmon resonance (SPR) and demonstrate that they can be modulated by the addition of millimolar concentrations of free amino acids. With CIC, we determined the second osmotic virial cross-interaction coefficient (B23) as a proxy for the interaction strength between two different proteins. We perform SPR experiments to establish the binding affinity between the same proteins. With CIC, we show that the amino acids proline, glutamine, and arginine render the protein cross-interactions more repulsive or equivalently less attractive. Specifically, we measured B23 between lysozyme (Lys) and bovine serum albumin (BSA) and between Lys and protein isolates (whey and canola). We find that B23 increases when amino acids are added to the solution even at millimolar concentrations, corresponding to protein/ligand stoichiometric ratios as low as 1:1. With SPR, we show that the binding affinity between proteins can change by 1 order of magnitude when 10 mM glutamine is added. In the case of Lys and one whey protein isolate (WPI), it changes from the mM to the M range, thus by 3 orders of magnitude. Interestingly, this efficient modulation of the protein cross-interactions does not alter the protein's secondary structure. The capacity of amino acids to modulate protein cross-interactions at mM concentrations is remarkable and may have an impact across fields in particular for specific applications in the food or pharmaceutical industries.
Subject(s)
Amino Acids , Muramidase , Protein Binding , Serum Albumin, Bovine , Surface Plasmon Resonance , Serum Albumin, Bovine/chemistry , Serum Albumin, Bovine/metabolism , Amino Acids/chemistry , Amino Acids/metabolism , Muramidase/chemistry , Muramidase/metabolism , Animals , CattleABSTRACT
PURPOSE: Analyzed the associations of sedentary behavior (SB) measured by questionnaire and accelerometer, with cardiometabolic markers in adolescents. METHODS: Longitudinal study with 4 years of follow-up with adolescents from João Pessoa, Brazil. SB was measured using a questionnaire (305 adolescents: 54.5% females; age 11.7 [SD = 0.7]) and use of accelerometer (136 adolescents: 54.8% females; age 11.5 [SD = 0.7]). The cardiometabolic markers were body mass index, waist circumference, systolic and diastolic blood pressure, fasting glucose, total cholesterol, triglycerides, low-density lipoproteins and high-density lipoproteins (HDL-C), total cholesterol/HDL ratio, triglycerides/HDL ratio, and non-HDL-C. Generalized Estimating Equation analysis was used to for analyses. RESULTS: The average time in SB by the accelerometer was greater (average 8.3 [SD = 1.5], 8.8 [SD = 1.6], and 8.4 [SD = 1.9] h/d/wk) than observed in the questionnaire (on average 6.0 [SD = 4.1], 7.2 [SD = 4.9], and 6.6 [SD = 5.4] h/d/wk), in all years of the study, but without a significant increasing trend (P > .05) over time for both measures. There was a significant and positive association between SB measured by the questionnaire and SBP (ß = 0.148; 95% CI, 0.021-0.274). CONCLUSIONS: The SB generally does not seem to contribute to significant changes in cardiometabolic markers in adolescents, despite it being associated with increased systolic blood pressure levels.
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OBJECTIVE: To identify the difference in breast cancer mortality rates among young women according to countries' economic classification. METHODS: A systematic literature review included retrospective studies on breast cancer mortality rates in women aged 20 to 49 years. Databases used were PubMed, Web of Science, Scopus, and Virtual Health Library, with articles selected in English, Portuguese, and Spanish. The study selection and analysis were conducted by two pairs of researchers. Data from 54 countries were extracted, including 39 high-income, 12 upper-middle-income, and 3 lower-middle-income countries. A meta-analysis was performed with the quantitative data from two studies. RESULTS: Six articles met the inclusion criteria. Four were analyzed descriptively due to data diversity, and two were included in the meta-analysis. The pooled mortality rate for high-income countries was 10.2 per 100,000 women (95% CI: 9.8-10.6), while for upper-middle-income countries, it was 15.5 per 100,000 women (95% CI: 14.9-16.1). Lower-middle-income countries had a pooled mortality rate of 20.3 per 100,000 women (95% CI: 19.5-21.1). The decrease in mortality rates in high-income countries was statistically significant (p<0.05). CONCLUSION: Mortality rates for breast cancer among young women have decreased significantly in high-income countries but have increased in lower-income countries. This disparity underscores the impact of insufficient investment in preventive measures, health promotion, early diagnosis, and treatment on young women's mortality in lower-income countries.
Subject(s)
Breast Neoplasms , Developed Countries , Developing Countries , Humans , Female , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Prognosis , Young Adult , Adult , Survival Rate , Income , Middle Aged , Socioeconomic FactorsABSTRACT
This review highlights the nutritional content, phytochemical compounds, and biological properties of three unconventional food plants consumed in the Amazon: ora-pro-nóbis (Pereskia aculeata Mill.), taioba (Xanthosoma sagittifolium), and vitória-régia (Victoria amazonica). These plants show significant nutritional, functional, and economic potential, which can enhance the intake of daily nutrients, energy, and bioactive compounds. Ora-pro-nóbis is a rich source of caftaric acid, quercetin, and isorhamnetin; taioba contains syringic acid, caffeic acid, and quercetin; and vitória-régia shows cinnamic acid, caffeic acid, and sinapic acid in its composition. These compounds confer antioxidant, anticancer, antimicrobial, anti-inflammatory, analgesic, and antiproliferative properties on these plants. These unconventional plants can be exploited by the food industry as food and supplements and therapeutic plants to develop valuable products for food, cosmetics, pharmaceutical, and medical applications.
Subject(s)
Antioxidants , Nutritive Value , Phenols , Plants, Edible , Plants, Edible/chemistry , Antioxidants/pharmacology , Antioxidants/analysis , Phenols/analysis , Plant Extracts/pharmacology , Quercetin/pharmacology , Quercetin/analysis , Quercetin/analogs & derivatives , Coumaric Acids/analysis , Caffeic Acids/pharmacology , Humans , Cinnamates/analysis , Cinnamates/pharmacology , Phytochemicals/analysis , Phytochemicals/pharmacology , Animals , Anti-Infective Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Gallic Acid/analogs & derivativesABSTRACT
BACKGROUND: The World Health Organization (WHO) recommends that HIV treatment scale-up is accompanied by a robust assessment of drug resistance emergence and transmission. The WHO HIV Drug Resistance (HIVDR) monitoring and surveillance strategy includes HIVDR testing in adults both initiating and receiving antiretroviral therapy (ART). Due to limited information about HIVDR in Mozambique, we conducted two nationally representative surveys of adults initiating and receiving first-line ART regimes to better inform the HIV program. METHODS: We carried out a cross-sectional study between March 2017 and December 2019. Adults (older than 15 years) living with HIV (PLHIV) initiating ART or receiving first-line ART for between 9-15 months at 25 health facilities across all eleven provinces in Mozambique were included. Genotypic HIVDR was assessed on dried blood spots (DBS) when viral loads were ≥ 1000 copies/ml. Genotypic resistance for non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was determined using the Stanford HIV database algorithm 9.5 and calibrated population resistance tool 8.1. RESULTS: Of 828 participants -enrolled, viral load (VL) testing was performed on 408 initiators and 409 ART experienced. Unsuppressed VL was found in 68.1% 419 initiators and 18.8% (77/409) of the ART experienced. Of the 278 initiators and 70 ART experienced who underwent sequencing, 51.7% (144/278) and 75.7% (53/70) were sequenced successfully. Among the new initiators, pretreatment drug resistance (PDR) for NNRTI and PI was found in 16.0% (23/144) and 1.4% (2/144) of the participants, respectively. Acquired drug resistance (ADR) was found in 56.5% (30/53) of the ART-experienced participants of whom 24.5% (13/53) were resistant to both NRTI and NNRTI. CONCLUSION: High rates of PDR and ADR for NNRTI and ADR for NRTI were observed in our study. These findings support the replacement of NNRTIs with dolutegravir (DTG) but high levels of NRTI resistance in highly treatment-experienced individuals still require attention when transitioning to new regimens. Moreover, the study underlines the need for routine VL testing and HIVDR surveillance to improve treatment management strategies.
Subject(s)
Anti-HIV Agents , Drug Resistance, Viral , HIV Infections , HIV-1 , Heterocyclic Compounds, 3-Ring , Lamivudine , Oxazines , Pyridones , Tenofovir , Humans , Mozambique/epidemiology , HIV Infections/drug therapy , HIV Infections/virology , Male , Drug Resistance, Viral/genetics , Female , Adult , Cross-Sectional Studies , HIV-1/drug effects , HIV-1/genetics , Anti-HIV Agents/therapeutic use , Pyridones/therapeutic use , Middle Aged , Lamivudine/therapeutic use , Tenofovir/therapeutic use , Heterocyclic Compounds, 3-Ring/therapeutic use , Oxazines/therapeutic use , Young Adult , Piperazines/therapeutic use , Adolescent , Viral Load/drug effects , GenotypeABSTRACT
The present study aimed at investigating whether the hydroxychloroquine (HCQ) treatment would impact the neutralizing antibody production, viremia levels and the kinetics of serum soluble mediators upon planned 17DD-Yellow Fever (YF) primovaccination (Bio-Manguinhos-FIOCRUZ) of primary Sjögren's syndrome (pSS). A total of 34 pSS patients and 23 healthy controls (HC) were enrolled. The pSS group was further categorized according to the use of HCQ (HCQ and Non-HCQ). The YF-plaque reduction neutralization test (PRNT ≥1:50), YF viremia (RNAnemia) and serum biomarkers analyses were performed at baseline and subsequent time-points (Day0/Day3-4/Day5-6/Day7/Day14-D28). The pSS group showed PRNT titers and seropositivity rates similar to those observed for HC (GeoMean = 238 vs 440, p = .11; 82% vs 96%, p = .13). However, the HCQ subgroup exhibited lower seroconversion rates as compared to HC (GeoMean = 161 vs 440, p = .04; 69% vs 96%, p = .02) and Non-HQC (GeoMean = 161 vs 337, p = .582; 69% vs 94%, p = .049). No differences in YF viremia were observed amongst subgroups. Serum biomarkers analyses demonstrated that HCQ subgroup exhibited increased levels of CCL2, CXL10, IL-6, IFN-γ, IL1-Ra, IL-9, IL-10, and IL-2 at baseline and displayed a consistent increase of several biomarkers along the kinetics timeline up to D14-28. These results indicated that HCQ subgroup exhibited a deficiency in assembling YF-specific immune response elicited by 17DD-YF primovaccination as compared to Non-HCQ subgroup. Our findings suggested that hydroxychloroquine is associated with a decrease in the humoral immune response after 17DD-YF primovaccination.
Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , Hydroxychloroquine , Seroconversion , Sjogren's Syndrome , Yellow Fever , Humans , Hydroxychloroquine/therapeutic use , Sjogren's Syndrome/drug therapy , Sjogren's Syndrome/immunology , Female , Middle Aged , Male , Adult , Yellow Fever/immunology , Yellow Fever/prevention & control , Antibodies, Viral/blood , Antibodies, Neutralizing/blood , Yellow Fever Vaccine/immunology , Aged , Viremia/drug therapy , Viremia/immunology , Yellow fever virus/immunology , Cytokines/blood , Biomarkers/bloodABSTRACT
BACKGROUND: This study aimed to compare the overall prevalence, stratified by sex and age group of global physical activity (GPA), active commuting to school (ACS), and sedentary behavior (SB) among adolescents from ten Latin American countries, and to assess the correlation of Development Index with the indicators. METHODS: This research is grounded on data from the Global School-Based Student Health Survey (2009-2015) and the 2015 Brazilian National School Health Survey. The prevalence and 95% confidence intervals for GPA (≥5 d/wk), ACS (≥1 d/wk), and SB (>2 h/d) were calculated using the chi-square test to compare the sexes (male; female) and age group (≤13 y; 14 y; 15 y; ≥16 y). We also performed Pearson correlation analysis with the Human Development Index. RESULTS: The prevalence of indicators ranged from 16.1% to 28.2% for GPA, from 56.7% to 71.2% for ACS, and from 20.7% to 62.6% for SB. Boys generally had a higher prevalence of GPA and ACS, and girls had a higher prevalence of SB. The prevalence of the indicators by age group varied between countries, with significant differences observed in some, depending on each indicator. A positive correlation was observed between Human Development Index, GPA, and SB. CONCLUSION: Health promotion policies must include guidelines that encourage and promote a more active and less sedentary lifestyle among young people in Latin America, considering specific groups, the local socioeconomic context, and differences between countries.
Subject(s)
Exercise , Health Surveys , Schools , Sedentary Behavior , Transportation , Humans , Adolescent , Male , Female , Latin America , Transportation/methods , Students/statistics & numerical data , Sex Factors , Prevalence , Child , Brazil/epidemiologyABSTRACT
Faba bean ingredients are rich in proteins and good sources of calcium (Ca), although containing phytic acid (PA) molecules. PA, a polyphosphate compound, can affect the bioavailability of minerals/proteins through complex formation. This study evaluates the impact of two extraction processes, Alkaline Extraction-IsoElectric Precipitation (AE-IEP) and Sequential Extraction (SE), on the ability of faba bean globulin systems to bind added calcium ions. Increasing concentrations of CaCl2 were introduced into 2.5% (w/v) protein dispersions at pHs 4.5, 5.5, 6.5, and 7.5, and free Ca monitored. Near the isoelectric point of globulin (pH â¼ 4-5), Ca binding capacity was found to be low. At higher pHs, significant Ca chelation occurred, initially attributed to free PA binding sites, resulting in the formation of insoluble complexes and subsequent protein precipitation. The AE-IEP globulin fraction exhibited a higher Ca binding capacity than the SE globulin, attributed to its higher PA and lower initial Ca concentrations.
Subject(s)
Calcium , Globulins , Plant Proteins , Vicia faba , Calcium/chemistry , Calcium/metabolism , Vicia faba/chemistry , Vicia faba/metabolism , Hydrogen-Ion Concentration , Globulins/chemistry , Globulins/metabolism , Globulins/isolation & purification , Plant Proteins/chemistry , Plant Proteins/metabolism , Plant Proteins/isolation & purification , Protein Binding , Chemical Fractionation/methodsABSTRACT
Drug delivery selectivity is a challenge for cancer treatment. A hybrid pegylated pH-sensitive liposome-extracellular vesicle isolated from human breast cancer cell MDA-MB-231 was developed to investigate its in vitro activity against breast cancer cells of different molecular profiles to overcome this inconvenience. The hybrid nanosystem was produced by film hydration, and doxorubicin (DOX) was encapsulated in this system using the ammonium sulfate gradient method. The characterization of this hybrid nanosystem revealed a mean diameter of 140.20 ± 2.70 nm, a polydispersity index of 0.102 ± 0.033, an encapsulation efficiency of doxorubicin of 88.9% ± 2.4, and a great storage stability for 90 days at 4 °C. The fusion of extracellular vesicles with liposomes was confirmed by nanoflow cytometry using PE-conjugated human anti-CD63. This hybrid nanosystem demonstrated cytotoxicity against human breast cancer cell lines with different molecular subtypes, enhanced anti-migration properties, and exhibited similar cellular uptake to the free DOX treatment. Preliminary acute toxicity assessments using Balb/C female mice indicated a median lethal dose of 15-17.5 mg/kg, with no evidence of splenic, liver, heart, bone marrow, and renal damage at a dose of 15 mg/kg. These findings suggest the hybrid formulation as a versatile nanocarrier for the treatment of various breast cancer subtypes.
ABSTRACT
Oligodendrocyte progenitor cells (OPCs) represent a subtype of glia, giving rise to oligodendrocytes, the myelin-forming cells in the central nervous system (CNS). While OPCs are highly proliferative during development, they become relatively quiescent during adulthood, when their fate is strictly influenced by the extracellular context. In traumatic injuries and chronic neurodegenerative conditions, including those of autoimmune origin, oligodendrocytes undergo apoptosis, and demyelination starts. Adult OPCs become immediately activated; they migrate at the lesion site and proliferate to replenish the damaged area, but their efficiency is hampered by the presence of a glial scar-a barrier mainly formed by reactive astrocytes, microglia and the deposition of inhibitory extracellular matrix components. If, on the one hand, a glial scar limits the lesion spreading, it also blocks tissue regeneration. Therapeutic strategies aimed at reducing astrocyte or microglia activation and shifting them toward a neuroprotective phenotype have been proposed, whereas the role of OPCs has been largely overlooked. In this review, we have considered the glial scar from the perspective of OPCs, analysing their behaviour when lesions originate and exploring the potential therapies aimed at sustaining OPCs to efficiently differentiate and promote remyelination.
Subject(s)
Cicatrix , Neuroglia , Oligodendrocyte Precursor Cells , Remyelination , Humans , Animals , Oligodendrocyte Precursor Cells/metabolism , Cicatrix/pathology , Neuroglia/metabolism , Neuroglia/pathology , Oligodendroglia/metabolism , Oligodendroglia/cytology , Myelin Sheath/metabolism , Cell DifferentiationABSTRACT
Amantadine (AMA) is a useful drug in neuronal disorders, but few studies have been performed to access its toxicological profile. Conversely, doxorubicin (Dox) is a well-known antineoplastic drug that has shown neurotoxic effects leading to cognitive impairment. The aims of this study are to evaluate the cytotoxic, genotoxic, and mutagenic effects of AMA, as well as its possible protective actions against deleterious effects of Dox. The Salmonella/microsome assay was performed to assess mutagenicity while cytotoxicity and genotoxicity were evaluated in SH-SY5Y cells using MTT and comet assays. Possible modulating effects of AMA on the cytotoxicity, genotoxicity, and mutagenicity induced by Dox were evaluated through cotreatment procedures. Amantadine did not induce mutations in the Salmonella/microsome assay and decreased Dox-induced mutagenicity in the TA98 strain. AMA reduced cell viability and induced DNA damage in SH-SY5Y cells. In cotreatment with Dox, AMA attenuated the cytotoxicity of Dox and showed an antigenotoxic effect. In conclusion, AMA does not induce gene mutations, although it has shown a genotoxic effect. Furthermore, AMA decreases frameshift mutations induced by Dox as well as the cytotoxic and genotoxic effects of Dox in SH-SY5Y cells, suggesting that AMA can interfere with Dox mutagenic activity and attenuate its neurotoxic effects.
Subject(s)
Amantadine , Cell Survival , DNA Damage , Doxorubicin , Humans , Doxorubicin/toxicity , Cell Line, Tumor , Cell Survival/drug effects , Amantadine/pharmacology , Amantadine/toxicity , Amantadine/analogs & derivatives , DNA Damage/drug effects , Mutagens/toxicity , Antibiotics, Antineoplastic/toxicity , Mutagenicity TestsABSTRACT
Developing strong and simultaneously tough polymeric materials with excellent thermal stability and mechanical performance even under extreme temperatures is truly a challenge. In a disruptive progress, continuous polymeric yarns are developed with a combination of high tensile strength of (1145 ± 44) MPa and ultrahigh toughness of (350 ± 24) J g-1 and high thermomechanical properties from -196 to 200 °C. The comprehensive thermomechanical performance of this yarn surpasses that of previously developed polymeric materials and dragline spider silks. The results demonstrate that the molecular structure of polyimide (PI) with the incorporation of flexible-rigid macromolecular, hierarchically spiral-oriented fibers, and high glass transition temperature (248 °C) are keys for the yarn's notable comprehensive performance in thermomechanical properties. The materials are ideal for technical components exposed to high thermomechanical loadings, such as those encountered in spacecraft or automotive engineering for safety-critical applications.
ABSTRACT
Conservation Units (CUs) tend to have a high richness of herbivorous insects, including gall-inducing insects. Despite this, gall surveys carried out in these environments are punctual and some units have never had their galls investigated, such as the Chapada Diamantina National Park, Bahia (Chapada Diamantina Parna). Aiming to reduce this gap and contribute to future studies in CUs, this study aimed to survey the galls of the Chapada Diamantina Parna, Lençóis, as well as to investigate trends in research on galls in CUs in Brazil. For that, collections were carried out on monthly trips for one year. Published gall surveys were compiled. A total of 107 morphotypes induced in 88 host species were recorded. Most galls are formed in leaves, globoid in shape, green in color, and induced by Cecidomyiidae. This park has a relatively high richness of galls compared to other CUs, demonstrating its importance in the conservation of gall-inducing insects. The results also revealed that the number of surveys has been increasing over the years and that the Southeast concentrates the largest number of studies, a region that also gathers the largest number of specialists, demonstrating a geographic bias in the data.