PDX Models in Theranostic Applications: Generation and Screening for B Cell Lymphoma of Human Origin.

This MIB guide briefly summarizes the generation of patient-derived xenografts (PDXs) and highlights the importance of validating PDX models for the presence of B cell lymphoma of human origin before their use in radiotheranostic applications. The use of this protocol will allow researchers to learn different methods for screening PDX models for Epstein-Barr virus (EBV)-infected B cell lymphoma.

Redox Homeostasis Disclosed in the Saltmarsh Plant Halimione portulacoides upon Short Waterborne Exposure to Inorganic Mercury.

The saltmarsh plant Halimione portulacoides was shortly exposed to realistic levels of inorganic mercury (iHg) with the aim of investigating the adaptative processes of the roots and leaves regarding redox homeostasis, physiology, and Hg accumulation. Plants were collected at a contaminated (CONT) and a reference (REF) site to address the interference of contamination backgrounds. The influence of major abiotic variables (i.e., temperature and light) was also examined. Total Hg levels, antioxidant enzymes, lipid peroxidation (LPO), and photosynthetic activity were analyzed after 2 and 4 h of exposure. A poor accumulation of Hg in the roots was noticed, and no translocation to the stems and leaves was found, but plants from the CONT site seemed more prone to iHg uptake (in winter). Despite this, antioxidant modulation in the roots and leaves was found, disclosing, in winter, higher thresholds for the induction of enzymatic antioxidants in CONT leaves compared to REF plants, denoting that the former are better prepared to cope with iHg redox pressure. Consistently, CONT leaves exposed to iHg had remarkably lower LPO levels. Exposure did not impair photosynthetic activity, pinpointing H. portulacoides' ability to cope with iHg toxicity under very-short-term exposure. Biochemical changes were noticed before enhancements in accumulation, reinforcing the relevance of these responses in precociously signaling iHg toxicity.

Correction: Cotovio et al. Regulatory Clearance and Approval of Therapeutic Protocols of Transcranial Magnetic Stimulation for Psychiatric Disorders. Brain Sci. 2023, 13, 1029.

Missing Citation [...].

Reducing motor evoked potential amplitude variability through normalization.

Background: Transcranial Magnetic Stimulation (TMS) is used for in vivo assessment of human motor cortical excitability, with application of TMS pulses over the motor cortex resulting in muscle responses that can be recorded with electromyography (EMG) as Motor Evoked Potentials (MEPs). These have been widely explored as potential biomarkers for neuropsychiatric disorders but methodological heterogeneity in acquisition, and inherent high variability, have led to constraints in reproducibility. Normalization, consisting in scaling the signal of interest to a known and repeatable measurement, reduces variability and is standard practice for between-subject comparisons of EMG. The effect of normalization on variability of MEP amplitude has not yet been explored and was assessed here using several methods. Methods: Three maximal voluntary isometric contractions (MVICs) and 40 MEPs were collected from the right hand in healthy volunteers, with a retest session conducted 4 to 8 weeks later. MEP amplitude was normalized using either external references (MVICs) or internal references (extreme MEPs). Iterative re-sampling of 30 normalized MEPs per subject was repeated 5,000 times to define, for each normalization method, distributions for between-subject coefficients of variation (CV) of the mean MEP amplitude. Intra-class correlation coefficients (ICC) were used to assess the impact of normalization on test­retest stability of MEP amplitude measurements. Results: In the absence of normalization, MEPs collected from the right hand of 47 healthy volunteers were within reported values regarding between-subject variability (95% confidence intervals for the CV: [1.0567,1.0577]) and showed good temporal stability (ICC = 0.77). Internal reference normalization substantially reduced between-subject variability, by values of up to 64%, while external reference normalization had no impact or increased between-subject variability. Normalization with the smallest references reduced test­retest stability, with use of the largest references resulting in slight reduction or improvement of ICCs. Internal reference normalization using the largest MEPs was found to be robust to several sensitivity analyses. Conclusion: Internal, but not external, reference normalization reduces between-subject variability of MEP amplitude, and has a minimal impact on within-subject variability when conducted with the largest references. Additional research is necessary to further validate these normalization methods toward potential use of MEPs as biomarkers of neuropsychiatric disorders.

Antimicrobial Resistance in Streptococcus pneumoniae before and after the Introduction of Pneumococcal Conjugate Vaccines in Brazil: A Systematic Review.

Streptococcus pneumoniae causes serious illnesses, such as pneumonia, bacteremia, and meningitis, mainly in immunocompromised individuals and those of extreme ages. Currently, pneumococcal conjugate vaccines (PCVs) are the best allies against pneumococcal diseases. In Brazil, the 10-valent and 13-valent PCVs have been available since 2010, but the threat of antimicrobial resistance persists and has been changing over time. We conducted a systematic review of the literature with works published since 2000, generating a parallel between susceptibility data on isolates recovered from colonization and invasive diseases before and after the implementation of PCVs for routine childhood use in Brazil. This systematic review was based on the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Literature Reviews and Meta-Analyses (PRISMA) guidelines. Despite the inclusion of PCVs at a large scale in the national territory, high frequencies of non-susceptibility to important drugs used in pneumococcal diseases are still observed, especially penicillin, as well as increasing resistance to macrolides. However, there are still drugs for which pneumococci have a comprehensive sensitivity profile.

Fast-Gelling Polyethylene Glycol/Polyethyleneimine Hydrogels Degradable by Visible-Light.

The treatment of burn wounds remains a clinical challenge due to the need for repeated dressings changes. Therefore, the development of a dressing system that can be atraumatically removed from the wound bed can be considered a breakthrough and improve treatment times. In this work, the development of an injectable, fast-gelling hydrogel is proposed that can change its mechanical properties when exposed to visible light. The hydrogels are prepared by a "click" amino-yne reaction between poly(ethylene glycol) (PEG) functionalized with propiolic acid and the amino groups of poly(ethyleneimine) (PEI). The hydrogels exhibit a fast gelation time, which can be adjusted by changing the weight percentage and molecular weight of the precursors. They also exhibit good swelling ability and adhesion to living tissues. More importantly, their mechanical properties changed upon irradiation with green light. This loss of properties is achieved by a 1 O2 -mediated mechanism, as confirmed by the degradation of the ß-aminoacrylate linker. Moreover, the in vitro cell compatibility results of the hydrogels and their degradation products show good cytocompatibility. Therefore, it is believed that these hydrogels can be considered as materials with great potential for an innovative strategy for the treatment of burn wounds.

Effect of hydrocolloid concentration in low-calorie orange jellies on preservation of bioactive compounds and antioxidant capacity.

The purpose of this paper was to avaliate of the concentration of hydrocolloids (low methoxyl pectin [LMP], guar gum [GG], and carrageenan gum [CG]) in low-calorie orange jellies in order to maximize the amount of bioactive compounds and antioxidant capacity, and to study the influence on degradation these compounds. A mixture design with seven tests was used to analyze the total phenolic compounds, ascorbic acid (vitamin C) and antioxidant capacity (ABTS, DPPH and ß-carotene/linoleic acid methods). The results were analyzed by response surface methodology and the Scott-Knott mean test at a significance level of 5% (p ≤ 0.05). In general, the regions containing 0.5% GG and 0.5% GC had higher levels of the variables under study, and this combination preserved the bioactive compounds and antioxidant activity of jellies in relation to that of orange juice.

Tarin-Loaded Nanoliposomes Activate Apoptosis and Autophagy and Inhibit the Migration of Human Mammary Adenocarcinoma Cells.

Background: Tarin, a lectin purified from Colocasia esculenta, promotes in vitro and in vivo immunomodulatory effects allied to promising anticancer and antimetastatic effects against human adenocarcinoma mammary cells. This makes this 47 kDa-protein a natural candidate against human breast cancer, a leading cause of death among women. Tarin encapsulated in pegylated nanoliposomes displays increased effectiveness in controlling the proliferation of a mammary adenocarcinoma lineage comprising MDA-MB-231 cells. Methods: The mechanisms enrolled in anticancer and antimetastatic responses were investigated by treating MDA-MB-231 cells with nano-encapsulated tarin at 72 µg/mL for up to 48h through flow cytometry and transmission electron microscopy (TEM). The safety of nano-encapsulated tarin towards healthy tissue was also assessed by the resazurin viability assay, and the effect of nanoencapsulated tarin on cell migration was evaluated by scratch assays. Results: Ultrastructural analyses of MDA-MB-231 cells exposed to nanoencapsulated tarin revealed the accumulation of autophagosomes and damaged organelles, compatible with autophagy-dependent cell death. On the other hand, the flow cytometry investigation detected the increased occurrence of acidic vacuolar organelles, a late autophagosome trait, along with the enhanced presence of apoptotic cells, activated caspase-3/7, and cell cycle arrest at G0/G1. No deleterious effects were observed in healthy fibroblast cells following tarin nanoencapsulated exposition, in contrast to reduced viability in cells exposed to free tarin. The migration of MDA-MB-231 cells was inhibited by nano-encapsulated tarin, with delayed movement by 24 h compared to free tarin. Conclusion: The nanoliposome formulation delivers tarin in a delayed and sustained manner, as evidenced by the belated and potent antitumoral and anti-migration effects on adenocarcinoma cells, with no toxicity to healthy cells. Although further investigations are required to fully understand antitumorigenic tarin mechanisms, the activation of both apoptotic and autophagic machineries along with the caspase-3/7 pathway, and cell cycle arrest may comprise a part of these mechanisms.

In Vivo Biorthogonal Antibody Click for Dual Targeting and Augmented Efficacy in Cancer Treatment.

Antibody-drug conjugates (ADCs) have emerged as promising therapeutics for cancer treatment; however, their effectiveness has been limited by single antigen targeting, potentially leading to resistance mechanisms triggered by tumor compensatory pathways or reduced expression of the target protein. Here, we present antibody-ADC click, an approach that harnesses bioorthogonal click chemistry for in vivo dual receptor targeting, irrespective of the levels of the tumor's expression of the ADC-targeting antigen. Antibody-ADC click enables targeting heterogeneity and enhances antibody internalization and drug delivery inside cancer cells, resulting in potent toxicity. We conjugated antibodies and ADCs to the bioorthogonal click moieties tetrazine (Tz) and trans-cyclooctene (TCO). Through sequential antibody administration in living biological systems, we achieved dual receptor targeting by in vivo clicking of antibody-TCO with antibody-Tz. We show that the clicked antibody therapy outperformed conventional ADC monotherapy or antibody combinations in preclinical models mimicking ADC-eligible, ADC-resistant, and ADC-ineligible tumors. Antibody-ADC click enables in vivo dual-antigen targeting without extensive antibody bioengineering, sustains tumor treatment, and enhances antibody-mediated cytotoxicity.

Repercussions of SARS-CoV-2 infection and the pandemic on birth routes: a cross-sectional study.

OBJECTIVE: To assess the repercussions of SARS-CoV-2 infection (suspected or confirmed) and the context of the pandemic on the birth route and humanized assistance during childbirth. METHOD: Cross-sectional epidemiological study, nested within a cohort and comparative with the research "Birth in Belo Horizonte: Survey on Childbirth and Delivery".The medical records of three reference maternity hospitals in Belo Horizonte were assessed, with a final sample of 1,682 pregnant women, in the months of May, June and July 2020. A descriptive analysis was carried out, with absolute and relative frequency, and a comparative one, with a Pearson's chi-square test. RESULTS: It was observed that 2.02% of pregnant women were infected with SARS-CoV-2.Before the pandemic, out of a total of 390 pregnant women, 74.10% gave birth vaginally.During a pandemic, among infected women, 51.61% gave birth via cesarean section and 48,39% via vaginal delivery;among uninfected, 26.99% cesarean sections and 73.01% vaginaldeliveries. CONCLUSION: There was an increase in the percentage of cesarean sections and a possible influence of the pandemic on the rates of indication of cesarean sections at the time of admission to the maternity ward.

PET and Optical Imaging of Caveolin-1 in Gastric Tumors.

Previous studies have suggested tumoral caveolin-1 (CAV1) as a predictive biomarker for the response to anti-HER2 antibody drug therapies in gastric tumors. In this study, radiolabeled and fluorescently labeled anti-CAV1 antibodies were developed and tested as an immunoPET or optical imaging agent to detect CAV1 in HER2-positive/CAV1-high NCIN87 gastric tumors. The expression of CAV1 receptors in NCIN87 gastric tumors and nontumor murine organs was determined by Western blot. Binding assays were performed to validate the anti-CAV1 antibody specificity for CAV1-expressing NCIN87 cancer cells. Subcutaneous and orthotopic NCIN87 xenografts were used for PET imaging and ex vivo biodistribution of the radioimmunoconjugate. Additional HER2-PET and CAV1-optical imaging was also performed to determine CAV1 in the HER2-positive tumors. 89Zr-labeled anti-CAV1 antibody was able to bind to CAV1-expressing NCIN87 cells with a Bmax value of 2.7 × 103 CAV1 receptors/cell in vitro. ImmunoPET images demonstrated the localization of the antibody in subcutaneous NCIN87 xenografts. In the orthotopic model, CAV1 expression was also observed by optical imaging in the HER2-positive tumors previously imaged with HER2-PET. Ex vivo biodistribution analysis further confirmed these imaging results. The preclinical data from this study demonstrate the potential of using CAV1-PET and optical imaging for detecting gastric tumors.

Influence of genetics on the occurrence of enamel hypomineralization affecting permanent and primary teeth: A scoping review.

BACKGROUND: Molar incisor hypomineralization (MIH) is prevalent worldwide and is a challenge for clinicians who provide oral care to children. Molar incisor hypomineralization has been considered a multifactorial disturbance that results from a combination of environmental and genetic factors. AIM: This scoping review followed the Joanna Briggs Institute protocol and aimed to identify the available evidence of the genetic influence on the etiology of MIH. DESIGN: The search strategy was conducted in multiple databases, including PubMed, BVS, Embase, Web of Science, and Scopus. Two trained reviewers, requiring a third reviewer in case of disagreements, collected evidence. RESULTS: Of 563 retrieved studies, 17 were included in the review. From 14 studies performed in humans, 10 investigated DNA polymorphisms, one analyzed DNA methylation, one aimed model of inheritance, and two focused on the phenotype in twins or in the family. Three animal studies were based on the null expression of genes. CONCLUSION: This scoping review, based on the studies that used different methodologies, reinforces the hypothesis of a genetic contribution to the multifactorial etiology of MIH. The available data are limited in terms of size and origin of the samples. Hence, further genetic studies are still required.

The IgA of hares (Lepus sp.) and rabbit confirms that the leporids IgA explosion is old and reveals a new case of trans-species polymorphism.

Background: Immunoglobulin A (IgA) is the mammalian mucosal antibody, providing an important line of defense against pathogens. With 15 IgA subclasses, the European rabbit has an extremely complex IgA system, strikingly more complex than most other mammals, which have only one IgA or, in the case of hominoids, two IgA subclasses. Similar to the two hominoid primate IGHA genes, the expansion of the rabbit IGHA genes appears to have begun in an ancestral lagomorph since multiple IgA copies were found by Southern blot analysis for the genera Sylvilagus, Lepus, and Ochotona. Results: To gain a better insight into the extraordinary lagomorph IgA evolution, we sequenced, for the first time, expressed IgA genes for two Lepus species, L. europaeus and L. granatensis. These were aligned with the 15 rabbit IgA isotypes, and evolutionary analyses were conducted. The obtained phylogenetic tree shows that the Lepus IgA sequences cluster with and among the rabbit IgA isotypes, and the interspecies and intraspecies nucleotide genetic distances are similar. A comparison of the amino acid sequences of the Lepus and rabbit IgA confirms that there are two trans-species polymorphisms and that the rabbit and Lepus sequences share a common genetic pool. In fact, the main differences between the studied leporids IgAs reside in the characteristics of the hinge region. Conclusion: The Lepus IgA sequences we have obtained strongly suggest that the great expansion of the leporid IGHA genes occurred in a common ancestral species and was then maintained in the descendants. A strong selective pressure caused the extraordinary expansion of the IGHA genes but then subsided, leading to the maintenance of the acquired polymorphisms in the descendants, with little subsequent divergence. This is a unique evolutionary pattern in which an ancient gene expansion has been maintained for approximately 18 million years.

Antiprotozoal Activity of Benzoylthiourea Derivatives against Trypanosoma cruzi: Insights into Mechanism of Action.

For decades, only two nitroheterocyclic drugs have been used as therapeutic agents for Chagas disease. However, these drugs present limited effectiveness during the chronic phase, possess unfavorable pharmacokinetic properties, and induce severe adverse effects, resulting in low treatment adherence. A previous study reported that N-(cyclohexylcarbamothioyl) benzamide (BTU-1), N-(tert-butylcarbamothioyl) benzamide (BTU-2), and (4-bromo-N-(3-nitrophenyl) carbamothioyl benzamide (BTU-3) present selective antiprotozoal activity against all developmental forms of Trypanosoma cruzi Y strain. In this study, we investigated the mechanism of action of these compounds through microscopy and biochemical analyses. Transmission electron microscopy analysis showed nuclear disorganization, changes in the plasma membrane with the appearance of blebs and extracellular arrangements, intense vacuolization, mitochondrial swelling, and formation of myelin-like structures. Biochemical results showed changes in the mitochondrial membrane potential, reactive oxygen species content, lipid peroxidation, and plasma membrane fluidity. In addition, the formation of autophagic vacuoles was observed. These findings indicate that BTU-1, BTU-2, and BTU-3 induced profound morphological, ultrastructural, and biochemical alterations in epimastigote forms, triggering an autophagic-dependent cell death pathway.

A review on aquatic toxins - Do we really know it all regarding the environmental risk posed by phytoplankton neurotoxins?

Aquatic toxins are potent natural toxins produced by certain cyanobacteria and marine algae species during harmful cyanobacterial and algal blooms (CyanoHABs and HABs, respectively). These harmful bloom events and the toxins produced during these events are a human and environmental health concern worldwide, with occurrence, frequency and severity of CyanoHABs and HABs being predicted to keep increasing due to ongoing climate change scenarios. These contexts, as well as human health consequences of some toxins produced during bloom events have been thoroughly reviewed before. Conversely, the wider picture that includes the non-human biota in the assessment of noxious effects of toxins is much less covered in the literature and barely covered by review works. Despite direct human exposure to aquatic toxins and related deleterious effects being responsible for the majority of the public attention to the blooms' problematic, it constitutes a very limited fraction of the real environmental risk posed by these toxins. The disruption of ecological and trophic interactions caused by these toxins in the aquatic biota building on deleterious effects they may induce in different species is paramount as a modulator of the overall magnitude of the environmental risk potentially involved, thus necessarily constraining the quality and efficiency of the management strategies that should be placed. In this way, this review aims at updating and consolidating current knowledge regarding the adverse effects of aquatic toxins, attempting to going beyond their main toxicity pathways in human and related models' health, i.e., also focusing on ecologically relevant model organisms. For conciseness and considering the severity in terms of documented human health risks as a reference, we restricted the detailed revision work to neurotoxic cyanotoxins and marine toxins. This comprehensive revision of the systemic effects of aquatic neurotoxins provides a broad overview of the exposure and the hazard that these compounds pose to human and environmental health. Regulatory approaches they are given worldwide, as well as (eco)toxicity data available were hence thoroughly reviewed. Critical research gaps were identified particularly regarding (i) the toxic effects other than those typical of the recognized disease/disorder each toxin causes following acute exposure in humans and also in other biota; and (ii) alternative detection tools capable of being early-warning signals for aquatic toxins occurrence and therefore provide better human and environmental safety insurance. Future directions on aquatic toxins research are discussed in face of the existent knowledge, with particular emphasis on the much-needed development and implementation of effective alternative (eco)toxicological biomarkers for these toxins. The wide-spanning approach followed herein will hopefully stimulate future research more broadly addressing the environmental hazardous potential of aquatic toxins.

Biodistribution and intestinal inflammatory response following voluntary oral intake of silver nanoparticles by C57BL/6J mice.

Silver nanoparticles (AgNP) are among the most widely commercialized nanomaterials globally, with applications in medicine and the food industry. Consequently, the increased use of AgNP in the food industry has led to an unavoidable rise  in human exposure to these nanoparticles. Their widespread use raises concerns about potential hazards to human health, specifically their intestinal pro-inflammatory effects. Thus, the main objective of this study was to evaluate the biological effects of two subacute doses of 5 nm polyvinylpyrrolidone (PVP)-AgNP in C57BL/6J mice. One mg/kg body weight or 10 mg/kg bw was provided once a day for 14 days, using a new technology (HaPILLness) that allows voluntary, stress-free, and accurate oral dosing. It was observed that after oral ingestion, while AgNP is biodistributed throughout the entire organism, most of the ingested dose is excreted in the feces. The passage and accumulation of AgNP throughout the intestine instigated a prominent inflammatory response, marked by significant histological, vascular, and cellular transformations. This response was driven by the activation of the nuclear factor-кB (NF-кB) inflammatory pathway, ultimately leading to the generation of multiple cytokines and chemokines.

Characterization of Thermo-Mechanical and Chemical Properties of Polypropylene/Hemp Fiber Biocomposites: Impact of Maleic Anhydride Compatibilizer and Fiber Content.

This article presents a comprehensive study on the physical, mechanical, thermal, and chemical properties of polypropylene (PP) composites reinforced with hemp fibers (HF) and compatibilized with maleic anhydride (MAPP). The composites were processed using a twin-screw extruder, followed by hot compression at 190 °C. Subsequently, the composites were analyzed using Izod impact and Shore D hardness tests to evaluate their mechanical properties. Thermal properties were investigated through differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), while X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) were employed to study their chemical properties. Additionally, a statistical analysis was conducted to compare the average results of the impact and hardness tests. XRD analysis revealed that the addition of HF and MAPP led to the disappearance of peaks corresponding to the beta phase in pure PP. Hemp fibers exhibited an impressive crystallinity of 82.10%, surpassing other natural fibers, and had a significant molecular orientation angle (MFA) of 6.06°, making them highly desirable for engineering applications. The crystallite size was observed to be relatively large, at 32.49 nm. FTIR analysis demonstrated strong interactions between the fiber, compatibilizing agent, and polymer matrix. TGA tests showed that the addition of 5 and 10 wt.% MAPP resulted in complete degradation of the composites, similar to pure PP. DSC analyses indicated a reduction in crystallinity (Xc) due to the incorporation of HF and MAPP. Shore D hardness tests revealed an increase in hardness with the addition of 5 wt.% MAPP, while a steep decline in this property was observed with 10 wt.% MAPP. In terms of impact resistance, fractions of 3 and 5 wt.% MAPP in the composites exhibited improved performance compared to the pure polymer. Analysis of variance (ANOVA) was employed to ensure the statistical reliability of the mechanical test results. This comprehensive study sheds light on the diverse properties of PP composites reinforced with hemp fibers and compatibilized with MAPP, emphasizing their potential as sustainable materials for engineering applications. The results contribute to the understanding of the structural and functional aspects of these composites, guiding future research and developments in the field.

Regulatory Clearance and Approval of Therapeutic Protocols of Transcranial Magnetic Stimulation for Psychiatric Disorders.

Non-invasive brain stimulation techniques (NIBS) have been widely used in both clinical and research contexts in neuropsychiatry. They are safe and well-tolerated, making NIBS an interesting option for application in different settings. Transcranial magnetic stimulation (TMS) is one of these strategies. It uses electromagnetic pulses for focal modulate ion of neuronal activity in brain cortical regions. When pulses are applied repeatedly (repetitive transcranial magnetic stimulation-rTMS), they are thought to induce long-lasting neuroplastic effects, proposed to be a therapeutic mechanism for rTMS, with efficacy and safety initially demonstrated for treatment-resistant depression (TRD). Since then, many rTMS treatment protocols emerged for other difficult to treat psychiatric conditions. Moreover, multiple clinical studies, including large multi-center trials and several meta-analyses, have confirmed its clinical efficacy in different neuropsychiatric disorders, resulting in evidence-based guidelines and recommendations. Currently, rTMS is cleared by multiple regulatory agencies for the treatment of TRD, depression with comorbid anxiety disorders, obsessive compulsive disorder, and substance use disorders, such as smoking cessation. Importantly, current research supports the potential future use of rTMS for other psychiatric syndromes, including the negative symptoms of schizophrenia and post-traumatic stress disorder. More precise knowledge of formal indications for rTMS therapeutic use in psychiatry is critical to enhance clinical decision making in this area.

Toxicological profile of the Hymenaea courbaril stem bark hydroalcoholic extract using in vitro bioassays and an alternative in vivo Caenorhabditis elegans model.

Hymenaea genus has been used in folk medicine in Brazil, but few studies investigated its toxicity profile. Thus, the aim of this study was to determine toxicological parameters of Hymenaea courbaril stem bark hydroalcoholic extract by utilizing three cell lines including murine macrophages (RAW 264.7), mouse fibroblast cells (L929) and human lung fibroblast (MRC-5), as well as Salmonella/microsome assay, and in vivo Caenorhabditis elegans model. The predominant detected phytoconstituents in the extract were coumarins, flavonoids, phenolics, tannins and saponins and by HPLC analysis, astilbin (AST) was found to be the main component. The DPPH assay demonstrated that H. courbaril hydroalcoholic extract exhibited potent antioxidant activity, with an IC50 of 3.12 µg/ml. The extract at concentrations of 400 and 800 µg/ml decreased cell viability 48 hr after treatment in L929 and MRC-5 cell lines. In the Raw 264.7 strain, just the highest concentration (800 µg/ml) lowered cell viability within 48 hr following exposure. The concentration of 100 µg/ml did not markedly affect cell viability in the trypan blue assay. In the alkaline comet assay the extract was found to be non-genotoxic. In the Ames test, the extract exhibited low mutagenic potential without metabolic activation, since only the highest concentrations produced an effect. H. courbaril extract only affected the survival of C. elegans at concentrations of 800 and 1600 µl/ml. These findings demonstrate that H. courbaril extract appears to exert low toxicity as evidenced in vitro and mutagenicity assays; however, the biological relevance of the response of C. elegans survival to safety assessments needs further studies.

Associated risks with periodontal x-rays or CBCT scans: Are there any?

Periodontal and implant radiography, mainly including intra-oral peri-apical and cone beam computed tomography images, are crucial in the diagnosis and treatment planning process. However, radiation safety concerns have been a chronic concern over the years, leading to uncomfortable situations. It is therefore crucial to understand the actual radiation exposure to determine if the patients' fear of necessary diagnostic exams is justified. In this perspective article, we aimed to provide concise information on dental imaging exposure, risks, and benefits, comparing them to that of absorbed radiation from daily life activities; and secondarily, to help periodontists choose the best option for each case and become more confident in addressing patients' concerns and providing a summary of safety guidelines as a reference for them.