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1.
Int J Mol Sci ; 25(12)2024 Jun 14.
Article En | MEDLINE | ID: mdl-38928276

Hematological neoplasias are among the most common cancers worldwide, and the number of new cases has been on the rise since 1990, reaching 1 [...].


Biomarkers, Tumor , Hematologic Neoplasms , Humans , Hematologic Neoplasms/metabolism , Biomarkers, Tumor/metabolism , Molecular Targeted Therapy/methods
2.
Microb Cell Fact ; 23(1): 169, 2024 Jun 10.
Article En | MEDLINE | ID: mdl-38858677

BACKGROUND: In vitro expression involves the utilization of the cellular transcription and translation machinery in an acellular context to produce one or more proteins of interest and has found widespread application in synthetic biology and in pharmaceutical biomanufacturing. Most in vitro expression systems available are active at moderate temperatures, but to screen large libraries of natural or artificial genetic diversity for highly thermostable enzymes or enzyme variants, it is instrumental to enable protein synthesis at high temperatures. OBJECTIVES: Develop an in vitro expression system operating at high temperatures compatible with enzymatic assays and with technologies that enable ultrahigh-throughput protein expression in reduced volumes, such as microfluidic water-in-oil (w/o) droplets. RESULTS: We produced cell-free extracts from Thermus thermophilus for in vitro translation including thermostable enzymatic cascades for energy regeneration and a moderately thermostable RNA polymerase for transcription, which ultimately limited the temperature of protein synthesis. The yield was comparable or superior to other thermostable in vitro expression systems, while the preparation procedure is much simpler and can be suited to different Thermus thermophilus strains. Furthermore, these extracts have enabled in vitro expression in microfluidic droplets at high temperatures for the first time. CONCLUSIONS: Cell-free extracts from Thermus thermophilus represent a simpler alternative to heavily optimized or pure component thermostable in vitro expression systems. Moreover, due to their compatibility with droplet microfluidics and enzyme assays at high temperatures, the reported system represents a convenient gateway for enzyme screening at higher temperatures with ultrahigh-throughput.


Protein Biosynthesis , Thermus thermophilus , Transcription, Genetic , Thermus thermophilus/genetics , Thermus thermophilus/metabolism , Thermus thermophilus/enzymology , Microfluidics/methods , Cell-Free System , DNA-Directed RNA Polymerases/metabolism , DNA-Directed RNA Polymerases/genetics , Temperature , Hot Temperature , Bacterial Proteins/metabolism , Bacterial Proteins/genetics
3.
Sci Rep ; 14(1): 13817, 2024 06 15.
Article En | MEDLINE | ID: mdl-38879680

The nasal cavity of living mammals is a unique structural complex among tetrapods, acquired along a series of major morphological transformations that occurred mainly during the Mesozoic Era, within the Synapsida clade. Particularly, non-mammaliaform cynodonts document several morphological changes in the skull, during the Triassic Period, that represent the first steps of the mammalian bauplan. We here explore the nasal cavity of five cynodont taxa, namely Thrinaxodon, Chiniquodon, Prozostrodon, Riograndia, and Brasilodon, in order to discuss the main changes within this skull region. We did not identify ossified turbinals in the nasal cavity of these taxa and if present, as non-ossified structures, they would not necessarily be associated with temperature control or the development of endothermy. We do, however, notice a complexification of the cartilage anchoring structures that divide the nasal cavity and separate it from the brain region in these forerunners of mammals.


Fossils , Mammals , Skull , Turbinates , X-Ray Microtomography , Animals , Mammals/anatomy & histology , Fossils/anatomy & histology , Skull/anatomy & histology , Skull/diagnostic imaging , South America , Turbinates/anatomy & histology , Turbinates/diagnostic imaging , Biological Evolution , Nasal Cavity/anatomy & histology , Nasal Cavity/diagnostic imaging , Phylogeny
4.
Plants (Basel) ; 13(11)2024 May 31.
Article En | MEDLINE | ID: mdl-38891329

The use of dwarf plants in tomato breeding has provided several advantages. However, there are no identified dwarf plants (dd) containing the self-pruning habit (spsp). The aim of this work was to obtain future generations, characterize the germplasm, and select potential dwarf plants with a determinate growth habit to obtain Salad-type lines. The work was started by carrying out hybridization, followed by the first, second, and third backcrosses. Once F2BC3 seeds became available, the introgression of the self-pruning gene (spsp) into dwarf plants (dd) began. Three strains of normal architecture and a determinate growth habit were hybridized with two strains of dwarf size and an indeterminate growth habit, thus yielding four hybrids. Additionally, donor genotype UFU MC TOM1, the commercial cultivar Santa Clara, and the wild accession Solanum pennellii were used in the experiment. Agronomic traits, fruit quality, metabolomics, and acylsugars content were evaluated, and dwarf plants with a determinate growth habit were selected. Hybrid 3 exhibited the highest yields. Visual differences between determinate and indeterminate dwarf plant seedlings were observed. It is suggested to carry out five self-pollinations of the best dwarf plant determined and subsequent hybridization with homozygous lines of normal plant architecture and determinate growth habit to obtain hybrids.

5.
Int J Mol Sci ; 25(11)2024 May 27.
Article En | MEDLINE | ID: mdl-38892020

Doxorubicin is an effective drug for cancer treatment; however, cardiotoxicity limits its use. Cardiotoxicity pathophysiology is multifactorial. GLP-1 analogues have been shown to reduce oxidative stress and inflammation. In this study, we evaluated the effect of pretreatment with liraglutide on doxorubicin-induced acute cardiotoxicity. A total of 60 male Wistar rats were allocated into four groups: Control (C), Doxorubicin (D), Liraglutide (L), and Doxorubicin + Liraglutide (DL). L and DL received subcutaneous injection of liraglutide 0.6 mg/kg daily, while C and D received saline for 2 weeks. Afterwards, D and DL received a single intraperitoneal injection of doxorubicin 20 mg/kg; C and L received an injection of saline. Forty-eight hours after doxorubicin administration, the rats were subjected to echocardiogram, isolated heart functional study, and euthanasia. Liraglutide-treated rats ingested significantly less food and gained less body weight than animals that did not receive the drug. Rats lost weight after doxorubicin injection. At echocardiogram and isolated heart study, doxorubicin-treated rats had systolic and diastolic function impairment. Myocardial catalase activity was statistically higher in doxorubicin-treated rats. Myocardial protein expression of tumor necrosis factor alpha (TNF-α), phosphorylated nuclear factor-κB (p-NFκB), troponin T, and B-cell lymphoma 2 (Bcl-2) was significantly lower, and the total NFκB/p-NFκB ratio and TLR-4 higher in doxorubicin-treated rats. Myocardial expression of OPA-1, MFN-2, DRP-1, and topoisomerase 2ß did not differ between groups (p > 0.05). In conclusion, doxorubicin-induced cardiotoxicity is accompanied by decreased Bcl-2 and phosphorylated NFκB and increased catalase activity and TLR-4 expression. Liraglutide failed to improve acute doxorubicin-induced cardiotoxicity in rats.


Cardiotoxicity , Doxorubicin , Liraglutide , Rats, Wistar , Animals , Liraglutide/pharmacology , Liraglutide/therapeutic use , Doxorubicin/adverse effects , Cardiotoxicity/etiology , Cardiotoxicity/metabolism , Male , Rats , Oxidative Stress/drug effects , Myocardium/metabolism , Myocardium/pathology , NF-kappa B/metabolism , Tumor Necrosis Factor-alpha/metabolism , Heart/drug effects
6.
Foods ; 13(11)2024 May 24.
Article En | MEDLINE | ID: mdl-38890864

Loop-mediated isothermal amplification, LAMP, is nowadays the most popular isothermal nucleic acid amplification technique, and as such, several commercial, ready-to-use master mixes have flourished. Unfortunately, independent studies to determine their performance are limited. The current study performed an independent evaluation of the existing ready-to-use commercial LAMP master mixes WarmStart® LAMP Kit, LavaLAMP™ DNA Master Mix, Saphir Bst Turbo GreenMaster, OptiGene Fast Master Mix ISO-004, and SynLAMP Mix. To reduce bias, three different genes, namely ttr (Salmonella spp.), rfbE (E. coli O157), and hly (Listeria monocytogenes), were targeted. The comparison was based on amplification speed, performance with decreasing DNA concentrations, and the effect of five typical LAMP reaction additives (betaine, DMSO, pullulan, TMAC, and GuHCl). Significant differences were observed among the different master mixes. OptiGene provided the fastest amplification and showed less detrimental effects associated with the supplements evaluated. Out of the chemicals tested, pullulan provided the best results in terms of amplification speed. It is noteworthy that the different additives impacted the master mixes differently. Overall, the current study provides insights into the performance of commercial LAMP master mixes, which can be of value for the scientific community to better select appropriate reagents when developing new methods.

7.
Biomater Adv ; 162: 213931, 2024 Jun 24.
Article En | MEDLINE | ID: mdl-38924805

Microbial colonization and development of infections in wounds is a sign of chronicity. The prevailing approach to manage and treat these wounds involves dressings. However, these often fail in effectively addressing infections, as they struggle to both absorb exudates and maintain optimal local moisture. The system here presented was conceptualized with a three-layer design: the outer layer made of a fibrous polycaprolactone (PCL) film, to act as a barrier for preventing microorganisms and impurities from reaching the wound; the intermediate layer formed of a sodium alginate (SA) hydrogel loaded with ampicillin (Amp) for fighting infections; and the inner layer comprised of a fibrous film of PCL and polyethylene glycol (PEG) for facilitating cell recognition and preventing wound adhesion. Thermal evaluations, degradation, wettability and release behavior testing confirmed the system resistance overtime. The sandwich demonstrated the capability for absorbing exudates (≈70 %) and exhibited a controlled release of Amp for up to 24 h. Antimicrobial testing was performed against Staphylococcus aureus and Escherichia coli, as representatives of Gram-positive and Gram-negative bacteria: >99 % elimination of bacteria. Cell cytotoxicity assessments showed high cytocompatibility levels, confirming the safety of the proposed sandwich system. Adhesion assays confirmed the system ease of detaching without mechanical effort (0.37 N). Data established the efficiency of the sandwich-like system, suggesting promising applications in infected wound care.

8.
World Allergy Organ J ; 17(5): 100906, 2024 May.
Article En | MEDLINE | ID: mdl-38818086

Hereditary angioedema (HAE) encompasses a group of diseases characterized by recurrent, genetically mediated angioedema associated with increased vascular permeability primarily due to bradykinin. The disease poses diagnostic challenges, leading to underdiagnosis and delayed therapy. Severe manifestations include laryngeal and intestinal angioedema, contributing to significant morbidity and mortality. If left undiagnosed, the estimated mortality rate of the disease ranges from 25% to 40% due to asphyxiation caused by laryngeal angioedema. There is a pressing need to enhance awareness of hereditary angioedema and its warning signs. The acronym "H4AE" may facilitate the memorization of these signs. This study comprehensively reviews clinical, laboratory, and physiopathological features of documented HAE subtypes. The study advocates for an improved HAE classification based on endotypes, building on the knowledge of angioedema pathophysiology. The proposed endotype classification of HAE offers a clear and applicable framework, encouraging advancements in disease understanding and classification.

9.
Comp Biochem Physiol C Toxicol Pharmacol ; 283: 109939, 2024 May 07.
Article En | MEDLINE | ID: mdl-38723702

Nanotechnology involves the utilization of nanomaterials, including polymeric nanocapsules (NCs) that are drug carriers. For modify drug release and stability, nanoformulations can feature different types of polymers as surface coatings: Polysorbate 80 (P80), Polyethylene glycol (PEG), Chitosan (CS) and Eudragit (EUD). Although nanoencapsulation aims to reduce side effects, these polymers can interact with living organisms, inducing events in the antioxidant system. Thus far, little has been described about the impacts of chronic exposure, with Drosophila melanogaster being an in vivo model for characterizing the toxicology of these polymers. This study analyzes the effects of chronic exposure to polymeric NCs with different coatings. Flies were exposed to 10, 50, 100, and 500 µL of NCP80, NCPEG, NCCS, or EUD. The survival rate, locomotor changes, oxidative stress markers, cell viability, and Nrf2 expression were evaluated. Between the coatings, NCPEG had minimal effects, as only 500 µL affected the levels of reactive species (RS) and the enzymatic activities of catalase (CAT) and glutathione S-transferase (GST) without reducing Nrf2 expression. However, NCEUD significantly impacted the total flies killed, RS, CAT, and Superoxide dismutase from 100 µL. In part, the toxicity mechanisms of these coatings can be explained by the imbalance of the antioxidant system. This research provided initial evidence on the chronic toxicology of these nanomaterials in D. melanogaster to clarify the nanosafety profile of these polymers in future nanoformulations. Further investigations are essential to characterize possible biochemical pathways involved in the toxicity of these polymeric coatings.

10.
Sci Rep ; 14(1): 11323, 2024 05 17.
Article En | MEDLINE | ID: mdl-38760468

Oxalate, a uremic toxin that accumulates in dialysis patients, is associated with cardiovascular disease. As oxalate crystals can activate immune cells, we tested the hypothesis that plasma oxalate would be associated with cytokine concentrations and cardiovascular outcomes in dialysis patients. In a cohort of 104 US patients with kidney failure requiring dialysis (cohort 1), we measured 21 inflammatory markers. As IL-16 was the only cytokine to correlate with oxalate, we focused further investigations on IL-16. We searched for associations between concentrations of IL-16 and mortality and cardiovascular events in the 4D cohort (1255 patients, cohort 2) and assessed further associations of IL-16 with other uremic toxins in this cohort. IL-16 levels were positively correlated with pOx concentrations (ρ = 0.39 in cohort 1, r = 0.35 in cohort 2) and were elevated in dialysis patients when compared to healthy individuals. No significant association could be found between IL-16 levels and cardiovascular events or mortality in the 4D cohort. We conclude that the cytokine IL-16 correlates with plasma oxalate concentrations and is substantially increased in patients with kidney failure on dialysis. However, no association could be detected between IL-16 concentrations and cardiovascular disease in the 4D cohort.


Cardiovascular Diseases , Heart Disease Risk Factors , Interleukin-16 , Renal Dialysis , Humans , Male , Female , Middle Aged , Interleukin-16/blood , Cardiovascular Diseases/blood , Cardiovascular Diseases/etiology , Aged , Oxalates/blood , Biomarkers/blood , Cohort Studies , Adult , Risk Factors , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/mortality
11.
Arthritis Rheumatol ; 2024 May 27.
Article En | MEDLINE | ID: mdl-38801195

OBJECTIVES: To evaluate the influence of anti-infliximab antibodies (anti-IFX) on 3 different points of care: response/tolerance to infliximab (IFX), tapering strategy, and in a subsequent treatment with a second tumor necrosis factor inhibitor (TNFi). METHODS: A prospective cohort of 60 radiographic axial spondyloarthritis (r-axSpA) patients under IFX were evaluated retrospectively regarding clinical/laboratorial data, IFX levels and anti-IFX, at baseline, after 6, 12-14, 22-24, 48-54, 96-102 weeks and before tapering or switching. RESULTS: Anti-IFX were detected in 27 (45%) patients, of whom 23 (85.1%) became positive in the first year of IFX treatment. In comparison to negative anti-IFX group, anti-IFX positive patients demonstrated the following: less use of methotrexate (MTX) as a concomitant treatment to IFX (5 [18.5%] vs. 14 [42.4%]; p=0.048); more infusion reactions at 22-24 weeks (p=0.020) and 48-54 weeks (p=0.034); more treatment failures (p=0.028) at 48-54 weeks; reduced overall IFX survival (p<0.001); and lower sustained responses (p=0.044). Of note, positive anti-IFX patients exhibited a shorter tapering survival (9.9 months [95% CI 4.0-15.8] vs 63.4 months [95% CI 27.9-98.8]; p=0.004) in comparison with negative anti-IFX patients. Conversely, for patients who failed IFX, positive anti-IFX patients had better clinical response to the second TNFi at 3 (15 [83.3%] vs. 3 [27.3%]; p=0.005) and 6 months (15 [83.3%] vs. 4 [36.4%]; p=0.017) than the negative anti-IFX patients after switching. CONCLUSIONS: This study provided novel data that anti-IFX is a parameter for reduced tapering survival, reinforcing its detection to guide clinical decision. Additionally, we confirmed in a long-term cohort the anti-IFX association with worse IFX performance and as predictor of 2nd TNFi good clinical response.

12.
J Food Sci ; 89(6): 3290-3305, 2024 Jun.
Article En | MEDLINE | ID: mdl-38767864

A better understanding of how emulsifier type could differently influence the behavior of nanostructured lipid carriers (NLC) under the gastrointestinal digestion process, as well as at the cellular level, is of utmost importance for the NLC-based formulations' optimization and risk assessment in the food field. In this study, NLC composed by fully hydrogenated soybean and high-oleic sunflower oils were prepared using soy lecithin (NLC Lß) or Tween 80 (NLC Tß) as an emulsifier. ß-Carotene was entrapped within NLC developed as a promising strategy to overcome ß-carotene's low bioavailability and stability. The effect of emulsifier type on the digestibility of ß-carotene-loaded NLC was evaluated using an in vitro dynamic digestion model mimicking peristalsis motion. The influence of ß-carotene-loaded NLC on cell viability was assessed using Caco-2 cells in vitro. NLC Tß remained stable in the gastric compartment, presenting particle size (PS) similar to the initial NLC (PS: 245.68 and 218.18 nm, respectively), while NLC Lß showed lower stability (PS > 1000 nm) in stomach and duodenum phases. NLC Tß also provided high ß-carotene protection and delivery capacity (i.e., ß-carotene bioaccessibility increased 10-fold). Based on the results of digestion studies, NLC Tß has shown better physical stability during the passage through the in vitro dynamic gastrointestinal system than NLC Lß. Moreover, the developed NLC did not compromise cell viability up to 25 µg/mL of ß-carotene. Thus, the NLC developed proved to be a biocompatible structure and able to incorporate and protect ß-carotene for further food applications. PRACTICAL APPLICATION: The findings of this study hold significant implications for industrial applications in terms of developing nanostructured lipid carriers from natural raw materials widely available and used to produce other lipid-based products in the food industry, as an alternative to synthetic ones. In this respect, the ß-carotene-loaded NLC developed in this study would find a great industrial application in the food industry, which is in constant search to develop functional foods capable of increasing the bioavailability of bioactive compounds.


Digestion , Emulsifying Agents , Nanostructures , beta Carotene , beta Carotene/chemistry , beta Carotene/pharmacokinetics , Caco-2 Cells , Humans , Emulsifying Agents/chemistry , Nanostructures/chemistry , Biological Availability , Drug Carriers/chemistry , Particle Size , Lipids/chemistry , Polysorbates/chemistry , Lecithins/chemistry , Cell Survival/drug effects , Sunflower Oil/chemistry
13.
J Proteome Res ; 23(6): 2148-2159, 2024 Jun 07.
Article En | MEDLINE | ID: mdl-38785273

Diverse proteomics-based strategies have been applied to saliva to quantitatively identify diagnostic and prognostic targets for oral cancer. Considering that these targets may be regulated by events that do not imply variation in protein abundance levels, we hypothesized that changes in protein conformation can be associated with diagnosis and prognosis, revealing biological processes and novel targets of clinical relevance. For this, we employed limited proteolysis-mass spectrometry in saliva samples to explore structural alterations, comparing the proteome of healthy control and oral squamous cell carcinoma (OSCC) patients with and without lymph node metastasis. Thirty-six proteins with potential structural rearrangements were associated with clinical patient features including transketolase and its interacting partners. Moreover, N-glycosylated peptides contribute to structural rearrangements of potential diagnostic and prognostic markers. Altogether, this approach utilizes saliva proteins to search for targets for diagnosing and prognosing oral cancer and can guide the discovery of potential regulated sites beyond protein-level abundance.


Mouth Neoplasms , Proteome , Saliva , Humans , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Mouth Neoplasms/diagnosis , Saliva/chemistry , Saliva/metabolism , Proteome/analysis , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/diagnosis , Female , Biomarkers, Tumor/metabolism , Male , Lymphatic Metastasis , Protein Conformation , Middle Aged , Prognosis , Proteomics/methods , Transketolase/metabolism , Aged , Mass Spectrometry , Salivary Proteins and Peptides/metabolism , Salivary Proteins and Peptides/analysis
14.
Homeopathy ; 2024 May 28.
Article En | MEDLINE | ID: mdl-38806149

Quality of life is a fundamental aspect of good health and differs from person to person, highlighting the importance of individualisation, which is one of the principles of homeopathic doctrine. Homeopathy aligns with the principles of the Brazilian public health system, reflecting the latter's ethos of universality, accessibility, care coordination, and comprehensiveness, offering a whole-person approach to health care. Homeopathy's individualised approach and expanded view of the health-disease process, with emphasis on healthy lifestyle guidance, contributes to the promotion of individual good health and quality of life. These attributes of homeopathy make it a valuable therapeutic option, with relevance to the health service of Brazil as well as to that of other countries across the world.

15.
J Conserv Dent Endod ; 27(4): 360-365, 2024 Apr.
Article En | MEDLINE | ID: mdl-38779215

Aim: To determine the effects of time and temperature on the viscosity of preheated composite resins. Materials and Methods: Eleven composite resins were heated to 60°C, and temperature analyses were performed at intervals of 1 min until they had cooled to 25°C. The permanent oscillatory shear test was performed at 25°C, 35°C, 50°C, and 60°C for three composite resins under a shear rate of 1s-1. One- and two-way analysis of variance were used for the analysis (α = 0.05). Results: There was no significant interaction between the composite resin and time (P = 0.9304), and only the main effect time was significantly different (P < 0.0001). A difference was observed between T0 and T6 (P < 0.001), but not after T7. The increase in temperature resulted in a viscosity reduction (P < 0.05). At 25°C, Beautifil II presented higher viscosity. Palfique LX5 showed a significant viscosity reduction with increasing temperature compared with the others (P < 0.05). For Beautifil II and Z100, there was no difference at temperatures of 50°C and 60°C, while for Palfique LX5, no statistical difference was observed at 35°C, 50°C, and 60°C. Conclusions: Ten minutes of preheating were sufficient to reach a temperature of 60°C, reducing viscosity by at least 84%. However, 5 min after removal, the composite resin cooled to room temperature. Clinical Significance: Preheating composite resin has potential benefits. To determine how this approach will work in clinical practice, it is important to define the effects of time and temperature in the protocol of this technique and understand its limitations.

16.
Gels ; 10(5)2024 Apr 25.
Article En | MEDLINE | ID: mdl-38786210

The transition from fossil fuels is in part limited by our inability to store energy at different scales. Batteries are therefore in high demand, and we need them to store more energy, be more reliable, durable and have less social and environmental impact. Silica-poly(vinyl alcohol) (PVA) composite aerogels doped with sodium perchlorate were synthesized as novel electrolytes for potential application in solid-state sodium batteries. The aerogels, synthesized by one-pot synthesis, are light (up to 214 kg m-3), porous (~85%), exhibit reduced shrinkage on drying (up to 12%) and a typical silica aerogel microstructure. The formation of a silica network and the presence of PVA and sodium perchlorate in the composite were confirmed by FTIR and TGA. The XRD analysis also shows that a predominantly amorphous structure is obtained, as crystalline phases of polymer and salt are present in a very reduced amount. The effects of increasing polymer and sodium salt concentrations on the ionic conductivity, assessed via electrochemical impedance spectroscopy, were studied. At a PVA concentration of 15% (w/w silica precursors), the sodium conduction improved significantly up to (1.1 ± 0.3) × 10-5 S cm-1. Thus, this novel material has promising properties for the envisaged application.

17.
Toxics ; 12(5)2024 Apr 30.
Article En | MEDLINE | ID: mdl-38787111

Introduction: Monoclonal antibodies (mAbs) are important therapeutics. However, the enhanced potential for aggregation has become a critical quality parameter during the production of mAbs. Furthermore, mAb aggregation may also present a potential health risk in a clinical setting during the administration of mAb therapeutics to patients. While the extent of immunotoxicity in patient populations is uncertain, reports show it can lead to immune responses via cell activation and cytokine release. In this study, an autologous in vitro skin test designed to predict adverse immune events, including skin sensitization, was used as a novel assay for the assessment of immunotoxicity caused by mAb aggregation. Material and Methods: Aggregation of mAbs was induced by a heat stress protocol, followed by characterization of protein content by analytical ultra-centrifugation and transmission electron microscopy, revealing a 4% aggregation level of total protein content. Immunotoxicity and potential skin sensitization caused by the aggregates, were then tested in a skin explant assay. Results: Aggregated Herceptin and Rituximab caused skin sensitization, as shown by histopathological damage (grade II-III positive response) together with positive staining for Heat Shock Protein 70 (HSP70). Changes in T cell proliferation were not observed. Cytokine analysis revealed a significant increase of IL-10 for the most extreme condition of aggregation (65 °C at pH3) and a trend for an overall increase of IFN-γ, especially in response to Rituximab. Conclusions: The skin explant assay demonstrated that aggregated mAbs showed adverse immune reactions, as demonstrated as skin sensitization, with histopathological grades II-III. The assay may, therefore, be a novel tool for assessing immunotoxicity and skin sensitization caused by mAb aggregation.

18.
Environ Int ; 186: 108597, 2024 Apr.
Article En | MEDLINE | ID: mdl-38579453

The growing body of evidence links exposure to particulate matter pollutants with an increased risk of neurodegenerative diseases. In the present study, we investigated whether diesel exhaust particles can induce neurobehavioral alterations associated with neurodegenerative effects on glutamatergic and dopaminergic neurons in Caenorhabditis elegans (C. elegans). Exposure to DEP at concentrations of 0.167 µg/cm2 and 1.67 µg/cm2 resulted in significant developmental delays and altered locomotion behaviour. These effects were accompanied by discernible alterations in the expressions of antioxidant genes sod-3 and gst-4 observed in transgenic strains. Behaviour analysis demonstrated a significant reduction in average speed (p < 0.001), altered paths, and decreased swimming activities (p < 0.01), particularly at mid and high doses. Subsequent assessment of neurodegeneration markers in glutamatergic (DA1240) and dopaminergic (BZ555) transgenic worms revealed notable glutamatergic neuron degeneration at 0.167 µg/cm2 (∼30 % moderate, ∼20 % advanced) and 1.67 µg/cm2 (∼28 % moderate, ∼24 % advanced, p < 0.0001), while dopaminergic neurons exhibited structural deformities (∼16 %) without significant degeneration in terms of blebs and breaks. Furthermore, in silico docking simulations suggest the presence of an antagonistic competitive inhibition induced by DEP in the evaluated neuro-targets, stronger for the glutamatergic transporter than for the dopaminergic receptor from the comparative binding affinity point of view. The results underscore DEP's distinctive neurodegenerative effects and suggest a link between locomotion defects and glutamatergic neurodegeneration in C. elegans, providing insights into environmental health risks assessment.


Caenorhabditis elegans , Dopaminergic Neurons , Vehicle Emissions , Animals , Caenorhabditis elegans/drug effects , Dopaminergic Neurons/drug effects , Vehicle Emissions/toxicity , Particulate Matter/toxicity , Animals, Genetically Modified , Glutamic Acid/metabolism , Locomotion/drug effects , Neurodegenerative Diseases/chemically induced , Air Pollutants/toxicity
19.
Sci Total Environ ; 927: 172227, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38582104

The sensory quality of drinking water, and particularly its taste and odor (T&O) is a key determinant of consumer acceptability, as consumers evaluate water by their senses. Some of the conventional treatment processes to control compounds which impart unpleasant T&O have limitations because of their low efficiency and/or high costs. Therefore, there is a great need to develop an effective process for removing T&O compounds without secondary concerns. The primary objective of this study was to assess for the first time the effectiveness of spirulina-based carbon materials in removing geosmin (GSM) and 2-methylisoborneol (2-MIB) from water, two commonly occurring natural T&O compounds. The efficiency of the materials to remove environmentally relevant concentrations of GSM and 2-MIB (ng L-1) from ultrapure and raw water was investigated using a sensitive headspace solid-phase microextraction coupled with gas chromatography mass spectrometry (HS-SPME-GC/MS) method. Moreover, the genotoxic and cytotoxic effects of the spirulina-based materials were assessed for the first time to evaluate their safety and their potential in the treatment of water for human consumption. Based on the results, spirulina-based materials were found to be promising for drinking water treatment applications, as they did not exert geno-cytotoxic effects on human cells, while presenting high efficiency in removing GSM and 2-MIB from water.


Drinking Water , Odorants , Spirulina , Taste , Water Pollutants, Chemical , Water Purification , Drinking Water/chemistry , Odorants/analysis , Water Pollutants, Chemical/analysis , Water Purification/methods , Naphthols , Humans , Camphanes , Adsorption , Solid Phase Microextraction/methods , Carbon , Gas Chromatography-Mass Spectrometry
20.
Dent J (Basel) ; 12(4)2024 Apr 01.
Article En | MEDLINE | ID: mdl-38668001

The dental treatment of patients with oral cavity and oropharyngeal squamous cell carcinoma (OOPSCC) may be challenging for dentists. This study aimed to characterize systemic changes in patients with OOPSCC undergoing dental treatment prior to cancer therapy, with a specific focus on laboratory assessments. The primary objectives included identifying potential adverse events, such as infections or bleeding, resulting from dental procedures. Additionally, the study aimed to correlate baseline patient characteristics with treatment-related toxicities. This was a prospective cohort study that included 110 OOPSCC patients referred to the Dental Oncology Service at São Paulo State Cancer Institute, Brazil, between November/2019 and December/2020. Comorbidities, sociodemographic data, medication in use, cancer treatment-related toxicities, and altered laboratory tests results were correlated. The most common comorbidities and altered laboratory results were hypertension, dyslipidemia, diabetes, as well as elevated levels of C-reactive protein, hemoglobin, and hematocrit. Toxicities exhibited a progressive pattern over time, encompassing oral mucositis (OM), xerostomia, dysphagia, dysgeusia, trismus, and radiodermatitis. No correlation between comorbidities and cancer treatment-related toxicities, a positive correlation between medications in use and OM, and a negative correlation between medications and dysgeusia were found. OM was associated with altered thyroxine (T4) and free thyroxine (FT4), calcium, urea, creatinine, alkaline phosphatase, and syphilis. Family income and housing were OM predictors. Altered T4/FT4/urea/calcium/alkaline phosphatase/creatinine/syphilis may be useful clinical predictors of OM. Despite the elevated prevalence of comorbidities and abnormal laboratory findings, dental treatment prior to cancer treatment yielded no adverse events.

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