Bridging the gap between models based on ordinary, delayed, and fractional differentials equations through integral kernels.

Evolution equations with convolution-type integral operators have a history of study, yet a gap exists in the literature regarding the link between certain convolution kernels and new models, including delayed and fractional differential equations. We demonstrate, starting from the logistic model structure, that classical, delayed, and fractional models are special cases of a framework using a gamma Mittag-Leffler memory kernel. We discuss and classify different types of this general kernel, analyze the asymptotic behavior of the general model, and provide numerical simulations. A detailed classification of the memory kernels is presented through parameter analysis. The fractional models we constructed possess distinctive features as they maintain dimensional balance and explicitly relate fractional orders to past data points. Additionally, we illustrate how our models can reproduce the dynamics of COVID-19 infections in Australia, Brazil, and Peru. Our research expands mathematical modeling by presenting a unified framework that facilitates the incorporation of historical data through the utilization of integro-differential equations, fractional or delayed differential equations, as well as classical systems of ordinary differential equations.

Inhibition of IL-1 Ameliorates Cardiac Dysfunction and Arrhythmias in a Murine Model of Kawasaki Disease.

BACKGROUND: Kawasaki disease (KD) is an acute febrile illness and systemic vasculitis often associated with cardiac sequelae, including arrhythmias. Abundant evidence indicates a central role for IL (interleukin)-1 and TNFα (tumor necrosis factor-alpha) signaling in the formation of arterial lesions in KD. We aimed to investigate the mechanisms underlying the development of electrophysiological abnormalities in a murine model of KD vasculitis. METHODS: Lactobacillus casei cell wall extract-induced KD vasculitis model was used to investigate the therapeutic efficacy of clinically relevant IL-1Ra (IL-1 receptor antagonist) and TNFα neutralization. Echocardiography, in vivo electrophysiology, whole-heart optical mapping, and imaging were performed. RESULTS: KD vasculitis was associated with impaired ejection fraction, increased ventricular tachycardia, prolonged repolarization, and slowed conduction velocity. Since our transcriptomic analysis of human patients showed elevated levels of both IL-1ß and TNFα, we asked whether either cytokine was linked to the development of myocardial dysfunction. Remarkably, only inhibition of IL-1 signaling by IL-1Ra but not TNFα neutralization was able to prevent changes in ejection fraction and arrhythmias, whereas both IL-1Ra and TNFα neutralization significantly improved vasculitis and heart vessel inflammation. The treatment of L casei cell wall extract-injected mice with IL-1Ra also restored conduction velocity and improved the organization of Cx43 (connexin 43) at the intercalated disk. In contrast, in mice with gain of function of the IL-1 signaling pathway, L casei cell wall extract induced spontaneous ventricular tachycardia and premature deaths. CONCLUSIONS: Our results characterize the electrophysiological abnormalities associated with L casei cell wall extract-induced KD and show that IL-1Ra is more effective in preventing KD-induced myocardial dysfunction and arrhythmias than anti-TNFα therapy. These findings support the advancement of clinical trials using IL-1Ra in patients with KD.

Evolution of ancient satellite DNAs in extant alligators and caimans (Crocodylia, Reptilia).

BACKGROUND: Crocodilians are one of the oldest extant vertebrate lineages, exhibiting a combination of evolutionary success and morphological resilience that has persisted throughout the history of life on Earth. This ability to endure over such a long geological time span is of great evolutionary importance. Here, we have utilized the combination of genomic and chromosomal data to identify and compare the full catalogs of satellite DNA families (satDNAs, i.e., the satellitomes) of 5 out of the 8 extant Alligatoridae species. As crocodilian genomes reveal ancestral patterns of evolution, by employing this multispecies data collection, we can investigate and assess how satDNA families evolve over time. RESULTS: Alligators and caimans displayed a small number of satDNA families, ranging from 3 to 13 satDNAs in A. sinensis and C. latirostris, respectively. Together with little variation both within and between species it highlighted long-term conservation of satDNA elements throughout evolution. Furthermore, we traced the origin of the ancestral forms of all satDNAs belonging to the common ancestor of Caimaninae and Alligatorinae. Fluorescence in situ experiments showed distinct hybridization patterns for identical orthologous satDNAs, indicating their dynamic genomic placement. CONCLUSIONS: Alligators and caimans possess one of the smallest satDNA libraries ever reported, comprising only four sets of satDNAs that are shared by all species. Besides, our findings indicated limited intraspecific variation in satellite DNA, suggesting that the majority of new satellite sequences likely evolved from pre-existing ones.

Satellite DNAs, heterochromatin, and sex chromosomes of the wattled jacana (Charadriiformes; Jacanidae): a species with highly rearranged karyotype.

Charadriiformes, which comprises shorebirds and their relatives, is one of the most diverse avian orders, with over 390 species showing a wide range of karyotypes. Here, we isolated and characterized the whole collection of satellite DNAs (satDNAs) at both molecular and cytogenetic levels of one of its representative species, named the wattled jacana (Jacana jacana), a species that contains a typical ZZ/ZW sex chromosome system and a highly rearranged karyotype. In addition, we also investigate the in situ location of telomeric and microsatellite repeats. A small catalog of 11 satDNAs was identified that typically accumulated on microchromosomes and on the W chromosome. The latter also showed a significant accumulation of telomeric signals, being (GA)10 the only microsatellite with positive hybridization signals among all the 16 tested ones. These current findings contribute to our understanding of the genomic organization of repetitive DNAs in a bird species with high degree of chromosomal reorganization contrary to the majority of bird species that have stable karyotypes.

The role of satellite DNAs in the chromosomal rearrangements and the evolution of the rare XY1Y2 sex system in Harttia (Siluriformes: Loricariidae).

The underlying processes behind the formation, evolution, and long-term maintenance of multiple sex chromosomes have been largely neglected. Among vertebrates, fishes represent the group with the highest diversity of multiple sex chromosome systems and, with six instances, the Neotropical fish genus Harttia stands out by presenting the most remarkable diversity. However, although the origin mechanism of their sex chromosome systems is well discussed, little is known about the importance of some repetitive DNA classes in the differentiation of multiple systems. In this work, by employing a combination of cytogenetic and genomic procedures, we evaluated the satellite DNA composition of H. carvalhoi with a focus on their role in the evolution, structure, and differentiation process of the rare XY1Y2 multiple sex chromosome system. The genome of H. carvalhoi contains a total of 28 satellite DNA families, with the A+T content ranging between 38,1 and 68,1% and the predominant presence of long satellites. The in situ hybridization experiments detected 15 satellite DNAs with positive hybridization signals mainly on centromeric and pericentromeric regions of almost all chromosomes or clustered on a few pairs. Five of them presented clusters on X, Y1, and/or Y2 sex chromosomes which were therefore selected for comparative hybridization in the other three congeneric species. We found several conserved satellites accumulated on sex chromosomes and also in regions that were involved in chromosomal rearrangements. Our results provide a new contribution of satellitome studies in multiple sex chromosome systems in fishes and represent the first satellitome study for a Siluriformes species.

Peri-implantitis with a potential axis to brain inflammation: an inferential review.

Peri-implantitis (PI) is a chronic, inflammatory, and infectious disease which affects dental implants and has certain similarities to periodontitis (PD). Evidence has shown that PD may be related to several types of systemic disorders, such as diabetes and insulin resistance, cardiovascular diseases, respiratory tract infections, adverse pregnancy outcomes, and neurological disorders. Furthermore, some types of bacteria in PD can also be found in PI, leading to certain similarities in the immunoinflammatory responses in the host. This review aims to discuss the possible connection between PI and neuroinflammation, using information based on studies about periodontal disorders, a topic whose connection with systemic alterations has been gaining the interest of the scientific community. Literature concerning PI, PD, and systemic disorders, such as neuroinflammation, brain inflammation, and neurological disorder, was searched in the PubMed database using different keyword combinations. All studies found were included in this narrative review. No filters were used. Eligible studies were analyzed and reviewed carefully. This study found similarities between PI and PD development, maintenance, and in the bacterial agents located around the teeth (periodontitis) or dental implants (peri-implantitis). Through the cardiovascular system, these pathologies may also affect blood-brain barrier permeability. Furthermore, scientific evidence has suggested that microorganisms from PI (as in PD) can be recognized by trigeminal fiber endings and start inflammatory responses into the trigeminal ganglion. In addition, bacteria can traverse from the mouth to the brain through the lymphatic system. Consequently, the immune system increases inflammatory mediators in the brain, affecting the homeostasis of the nervous tissue and vice-versa. Based on the interrelation of microbiological, inflammatory, and immunological findings between PD and PI, it is possible to infer that immunoinflammatory changes observed in PD can imply systemic changes in PI. This, as discussed, could lead to the development or intensification of neuroinflammatory changes, contributing to neurodegenerative diseases.

Rare Association Between Osteogenesis Imperfecta and Chondrosarcoma: Could a Pathogenic Variant in the Gene SERPINF1 Explain It?

Osteogenesis imperfecta (OI) type VI is a rare inherited disorder of the connective tissue caused by pathogenic variants in SERPINF1 gene, which encodes the pigment epithelium-derived factor (PEDF). PEDF is implicated in many biologic processes, including an anti-cancer role. This information is supported by in vitro and in vivo studies that evidenced its anti-angiogenic, anti-tumorigenic, and anti-metastatic properties. Although OI is related to skeletal changes such as bone fragility and deformities, as well as to other connective tissue defects, it does not represent a greater predisposition to the development of skeletal tumors. Here, we report on an adult with OI in which a deletion in exon 8 of the SERPINF1 gene (c.1152_1170del; p.384_390del) was identified. The patient presented popcorn calcification in both femoral epiphyses, but one of them presented radiological characteristics and evolution suspected of malignancy. Later, it was diagnosed as chondrosarcoma. This paper discusses that OI type VI patients may be at risk of developing some types of cancer.

Melatonin decreases plasma TNF-α and improves nonenzymatic antioxidant defence and insulin sensitivity in rats with apical periodontitis fed a high-fat diet.

AIM: To analyse the effects of melatonin (ME) treatment on oxidative stress and insulin resistance (IR) in rats with apical periodontitis (AP) fed a high-fat diet (HFD). METHODOLOGY: Eighty 60-day-old rats were divided into eight groups: control (CN), AP, HFD with AP (HFDAP), control with ME (CNME), AP with ME (APME), HFD with ME (HFDME) and HFD with AP+ME (HFDAPME). The animals from the HFD groups were fed a HFD throughout the experimental period. On day 7, the animals from the AP groups were subjected to experimental AP, and after 70 days, the ME groups were treated for 30 days. Glycaemia, insulinaemia, homeostatic model assessment for IR index, tumour necrosis factor-α (TNF-α), and interleukin-6 were analysed in plasma using biochemical tests and enzyme-linked immunosorbent assay. Thiobarbituric acid-reactive substances (TBARS), carbonyl protein (CP), superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione (GSH) and total antioxidant capacity (ferric reducing antioxidant power [FRAP]) were analysed in the gastrocnemius muscle. RESULTS: (1) Association of AP and HDF exacerbated IR, and ME treatment improved this alteration; (2) AP and HFD and their association showed increased TNF-α, and ME reversed it; (3) TBARS increased in the AP and HFDAP groups, and ME reversed only in the group with the association of disease and diet; (4) CP increased in all HFD groups and improved in the ME groups; (5) GSH activity decreased in all experimental groups, and ME increased this parameter only in the CN and AP groups; (6) FRAP did not change between the groups, but ME treatment increased its activity in the AP and HFD groups; (7) ME increased SOD in the CN and AP groups. CONCLUSION: Apical periodontitis and HFD promoted IR, and the association of AP with diet promoted IR exacerbation; this resistance might have been caused by an increase in TNF-α. AP promoted more intense changes in lipid oxidative damage than in protein oxidative damage. In non-enzymatic antioxidant defence, it was observed that both AP and HFD and their association promoted a decrease in GSH levels. Overall, ME treatment reversed changes such as oxidative stress and IR.

Antioxidants and cardioprotective effects of ethyl acetate fraction of Canavalia rosea leaves in myocardial ischemia-reperfusion injury.

Different degrees in the biological activities of Canavalia rosea had been previously reported . In this study, our group assessed the cardioprotective effects of the ethyl acetate fraction (EAcF) of the Canavalia rosea leaves. Firstly, it was confirmed, by in vitro approach, that the EAcF has high antioxidant properties due to the presence of important secondary metabolites, as flavonoids. In order to explore their potential protector against cardiovascular disorders, hearts were previously perfused with EAcF (300 µg.mL-1) and submitted to the global ischemia followed by reperfusion in Langendorff system. The present findings have demonstrated that EAcF restored the left ventricular developed pressure and decreased the arrhythmias severity index. Furthermore, EAcF significantly increased the glutathiones peroxidase activity with decreased malondialdehyde and creatine kinase levels. EAcF was effective upon neither the superoxide dismutase, glutationes reductase nor the catalase activities. In addition, the Western blot analysis revealed that ischemia-reperfusion injury significantly upregulates caspase 3 protein expression, while EAcF abolishes this effect. These results provide evidence that the EAcF reestablishes the cardiac contractility and prevents arrhythmias; it is suggested that EAcF could be used to reduce injury caused by cardiac reperfusion. However more clinical studies should be performed, before applying it in the clinic.

Melatonin decreases IRF-3 protein expression in the gastrocnemius muscle, reduces IL-1ß and LPS plasma concentrations, and improves the lipid profile in rats with apical periodontitis fed on a high-fat diet.

To evaluate the effects of melatonin (MEL) on the expression of toll-like receptor-4 (TLR4); myeloid differentiation primary response protein-88 (MyD88); TIR-domain-containing adapter-inducing interferon-ß (TRIF); IFN regulatory-factor-3 (IRF-3); nuclear factor kappa-B (NF-κB); plasma concentrations of interleukin-1ß (IL-1ß) and lipopolysaccharide (LPS); and lipid profile of rats with apical periodontitis (AP) fed on a high-fat diet (HFD). Eighty 60-day-old rats were divided into eight groups: control, AP, HFD, HFDAP, CNMEL, APMEL, HFDMEL and HFDAPMEL. HFD groups were fed on a HFD for 107 days. On day 7, experimental AP was induced in the AP groups, and after 70 days, MEL (5 mg/kg) was administered to the MEL groups for 30 days. Plasma concentrations of LPS and IL-1ß were analyzed using enzyme-linked immunosorbent assay, and the lipid profile was analyzed using biochemical tests. The expression of proteins involved in the TLR4 pathway (TLR4, MyD88, TRIF, IRF-3 and NF-κB) in the gastrocnemius muscle (GM) was evaluated using western blotting and qRT-PCR. Treatment with MEL decreased IRF-3 protein expression in GM and IL-1ß plasma concentration in the APMEL and HFDMEL groups. Reduction in LPS plasma concentration was reported only in the HFDMEL group. Additionally, a decrease in LDL and an increase in HDL were observed in the HFDMEL and HFDAPMEL groups. Treatment with MEL exhibited anti-inflammatory and anti-hyperlipidemic effects attributed to HFD and AP by reducing the plasma concentrations of IL-1ß and LPS in addition to reducing IRF-3 protein expression in the GM, which is associated with the production of inflammatory cytokines.

Cytogenetics Meets Genomics: Cytotaxonomy and Genomic Relationships among Color Variants of the Asian Arowana Scleropages formosus.

Scleropages formosus (Osteoglossiformes, Teleostei) represents one of the most valued ornamental fishes, yet it is critically endangered due to overexploitation and habitat destruction. This species encompasses three major color groups that naturally occur in allopatric populations, but the evolutionary and taxonomic relationships of S. formosus color varieties remain uncertain. Here, we utilized a range of molecular cytogenetic techniques to characterize the karyotypes of five S. formosus color phenotypes, which correspond to naturally occurring variants: the red ones (Super Red); the golden ones (Golden Crossback and Highback Golden); the green ones (Asian Green and Yellow Tail Silver). Additionally, we describe the satellitome of S. formosus (Highback Golden) by applying a high-throughput sequencing technology. All color phenotypes possessed the same karyotype structure 2n = 50 (8m/sm + 42st/a) and distribution of SatDNAs, but different chromosomal locations of rDNAs, which were involved in a chromosome size polymorphism. Our results show indications of population genetic structure and microstructure differences in karyotypes of the color phenotypes. However, the findings do not clearly back up the hypothesis that there are discrete lineages or evolutionary units among the color phenotypes of S. formosus, but another case of interspecific chromosome stasis cannot be excluded.

Chromosomal Rearrangements and Satellite DNAs: Extensive Chromosome Reshuffling and the Evolution of Neo-Sex Chromosomes in the Genus Pyrrhulina (Teleostei; Characiformes).

Chromosomal rearrangements play a significant role in the evolution of fish genomes, being important forces in the rise of multiple sex chromosomes and in speciation events. Repetitive DNAs constitute a major component of the genome and are frequently found in heterochromatic regions, where satellite DNA sequences (satDNAs) usually represent their main components. In this work, we investigated the association of satDNAs with chromosome-shuffling events, as well as their potential relevance in both sex and karyotype evolution, using the well-known Pyrrhulina fish model. Pyrrhulina species have a conserved karyotype dominated by acrocentric chromosomes present in all examined species up to date. However, two species, namely P. marilynae and P. semifasciata, stand out for exhibiting unique traits that distinguish them from others in this group. The first shows a reduced diploid number (with 2n = 32), while the latter has a well-differentiated multiple X1X2Y sex chromosome system. In addition to isolating and characterizing the full collection of satDNAs (satellitomes) of both species, we also in situ mapped these sequences in the chromosomes of both species. Moreover, the satDNAs that displayed signals on the sex chromosomes of P. semifasciata were also mapped in some phylogenetically related species to estimate their potential accumulation on proto-sex chromosomes. Thus, a large collection of satDNAs for both species, with several classes being shared between them, was characterized for the first time. In addition, the possible involvement of these satellites in the karyotype evolution of P. marilynae and P. semifasciata, especially sex-chromosome formation and karyotype reduction in P. marilynae, could be shown.

Biological Modification of Arrhythmogenic Substrates by Cell-Free Therapeutics.

Ventricular arrhythmias (VAs) represent a major cause of sudden cardiac death and afflict patients with heart failure from both ischaemic and non-ischaemic origins, and inherited cardiomyopathies. Current VA management, including anti-arrhythmic medications, autonomic modulation, implantable cardioverter-defibrillator implantation, and catheter ablation, remains suboptimal. Catheter ablation may even cause significant cardiomyocyte loss. Cell-based therapies and exosome treatment have been proposed as promising strategies to lessen cardiomyocyte death, modulate immune reaction, and reduce myocardial scarring, and, therefore, are potentially beneficial in treating VAs. In this review, we summarise the current cornerstones of VA management. We also discuss recent advances and ongoing evidence regarding cell-based and exosome therapy, with special attention to VA treatment.

Homogenisation for the monodomain model in the presence of microscopic fibrotic structures.

Computational models in cardiac electrophysiology are notorious for long runtimes, restricting the numbers of nodes and mesh elements in the numerical discretisations used for their solution. This makes it particularly challenging to incorporate structural heterogeneities on small spatial scales, preventing a full understanding of the critical arrhythmogenic effects of conditions such as cardiac fibrosis. In this work, we explore the technique of homogenisation by volume averaging for the inclusion of non-conductive micro-structures into larger-scale cardiac meshes with minor computational overhead. Importantly, our approach is not restricted to periodic patterns, enabling homogenised models to represent, for example, the intricate patterns of collagen deposition present in different types of fibrosis. We first highlight the importance of appropriate boundary condition choice for the closure problems that define the parameters of homogenised models. Then, we demonstrate the technique's ability to correctly upscale the effects of fibrotic patterns with a spatial resolution of 10 µm into much larger numerical mesh sizes of 100- 250 µm . The homogenised models using these coarser meshes correctly predict critical pro-arrhythmic effects of fibrosis, including slowed conduction, source/sink mismatch, and stabilisation of re-entrant activation patterns. As such, this approach to homogenisation represents a significant step towards whole organ simulations that unravel the effects of microscopic cardiac tissue heterogeneities.

A Hybrid Model for Cardiac Perfusion: Coupling a Discrete Coronary Arterial Tree Model with a Continuous Porous-Media Flow Model of the Myocardium.

This paper presents a novel hybrid approach for the computational modeling of cardiac perfusion, combining a discrete model of the coronary arterial tree with a continuous porous-media flow model of the myocardium. The constructive constrained optimization (CCO) algorithm captures the detailed topology and geometry of the coronary arterial tree network, while Poiseuille's law governs blood flow within this network. Contrast agent dynamics, crucial for cardiac MRI perfusion assessment, are modeled using reaction-advection-diffusion equations within the porous-media framework. The model incorporates fibrosis-contrast agent interactions and considers contrast agent recirculation to simulate myocardial infarction and Gadolinium-based late-enhancement MRI findings. Numerical experiments simulate various scenarios, including normal perfusion, endocardial ischemia resulting from stenosis, and myocardial infarction. The results demonstrate the model's efficacy in establishing the relationship between blood flow and stenosis in the coronary arterial tree and contrast agent dynamics and perfusion in the myocardial tissue. The hybrid model enables the integration of information from two different exams: computational fractional flow reserve (cFFR) measurements of the heart coronaries obtained from CT scans and heart perfusion and anatomy derived from MRI scans. The cFFR data can be integrated with the discrete arterial tree, while cardiac perfusion MRI data can be incorporated into the continuum part of the model. This integration enhances clinical understanding and treatment strategies for managing cardiovascular disease.

Clinical characteristics and outcomes of healthcare workers with COVID-19 pre- and postvaccination.

Vaccines are the most effective strategy to control the spread of coronavirus disease-2019 (COVID-19). Data on COVID-19 among healthcare workers (HCW) pre- and postvaccination are limited. This study aims to evaluate the clinical characteristics and outcomes of HCW with COVID-19 pre- and postvaccination. Retrospective cohort study. All HCWs with suspected COVID-19 were included. Demographic data, occupation, symptoms, work in COVID-19 area, and vaccination status were collected. There were 22 267 HCW visits for suspected COVID-19; 7879 (35.4%) tested positive, and 14 388 (64.6%) tested negative. Fever, cough, fatigue, and dyspnea were positive predictors of COVID-19, and sore throat, headache, coryza, work in a COVID-19 area, and COVID-19 vaccination were negative predictors. Of the total number of visits, 41.2% were from vaccinated HCW and 58.8% were from unvaccinated HCW. Among HCWs with COVID-19, 84 (1.1%) required hospitalization, 11 (0.1%) in an intensive care unit (ICU), with three (0.04%) deaths. Six hospitalizations occurred in vaccinated HCWs, being of short duration, with no need for ICU admission and no deaths. SARS-CoV-2 infection prevalence was high among HCW, and vaccinated HCW had fewer hospitalizations, need for ICU, and deaths. Therefore, vaccines may attenuate COVID-19 severity, and efforts must be concentrated to ensure adequate vaccination for HCW.

A New Exergy Disaggregation Approach for Complexity Reduction and Dissipative Equipment Isolation in Thermoeconomics.

Thermoeconomics connects thermodynamic and economic concepts in order to provide information not available in conventional energy and economic analysis. Most thermoeconomicists agree that exergy is the most appropriate thermodynamic magnitude to associate with cost. In some applications, exergy disaggregation is required. Despite the improvement in result accuracy, the modeling complexity increases. In recent years, different exergy disaggregation approaches have been proposed, mostly to deal with dissipative components and residues, despite all of them also increasing the complexity of thermoeconomics. This study aims to present a new thermoeconomic approach based on exergy disaggregation, which is able to isolate dissipative components with less modeling complexity. This approach, called the A&F Model, splits the physical exergy into two terms, namely, Helmholtz energy and flow work. These terms were evaluated from a thermoeconomic point of view, through a cost allocation in an ideal Carnot cycle, and they were also applied and compared with the UFS Model, through a cost allocation analysis, in a case study with an organic Rankine cycle-powered vapor compression refrigeration system. The complexity and computational effort reduction in the A&F are significantly less than in the UFS Model. This alternative approach yields consistent results.

Glutathione S-transferase activity in aquatic macrophytes and halophytes and biotransformation potential for biocides.

Glutathione S-transferase (GST) participates in the biotransformation of many xenobiotics including biocides. Its activity in plants is generally associated with their phytoremediation capabilities. Biocides have been used in agriculture and antifouling paints and they represent risks for the aquatic environment. The present study aimed to: (1) evaluate the basal GST activity in roots, stems, and leaves from thirteen plants (eleven aquatic macrophytes and two halophytes) collected at South Brazil wetlands; (2) estimate the biotransformation potential of Nothoscordum gracile for five biocides using competitive kinetic assays with 1-chloro-2,4-dinitrobenzene (CDNB), a typical GST substrate. The N. gracile, Spartina alterniflora and Cakile maritima presented the highest GST activities among the tested plants. The Lineweaver-Burk plot obtained from the GST competitive kinetic assays confirmed that the biocides chlorothalonil, 4,5-dichloro-N-octyl-3(2H)-isothiazolone (DCOIT), dichlofluanid, and diuron, but not irgarol, compete with the substrate CDNB for GST. Chlorothalonil and DCOIT showed the lowest IC20 values (11.1 and 10.6 µM, respectively), followed by dichlofluanid (38.6 µM) and diuron (353.1 µM). The inhibition of GST-CDNB activity by 100 nM biocide was higher for chlorothalonil, DCOIT, and dichlofluanid (46.5, 49.0, and 45.1%, respectively) than for diuron (6.5%) and irgarol (2.2%). The present study indicates plant species that have significant GST activity and could be potentially used for phytoremediation. The competitive kinetic tests suggest that among the five biocides that were tested, chlorothalonil, DCOIT, and dichlofluanid are probably preferred for biotransformation via GST in plant.

Effect of maternal apical periodontitis on the final step of insulin signalling and inflammatory pathway in the adult male offspring of rats.

AIM: To evaluate the final step of insulin signalling, inflammatory pathway (related to the inhibition of insulin signalling), peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) protein content and DNA methylation in the Slc2a4 gene promoter region in the skeletal muscle of adult male offspring of rats with apical periodontitis (AP) in a single tooth or in four teeth. METHODOLOGY: Female Wistar rats were distributed into three groups: a control group, a group with one tooth with AP and a group with four teeth with AP. Thirty days after induction of AP, female rats from all groups were mated with healthy male rats. When male offspring reached 75 days of age, the following analyses were performed in the gastrocnemius muscle (GM): insulin-stimulated Akt serine and threonine phosphorylation status; NF-κB p50 and p65 subunits phosphorylation status; GLUT4, TNF-α and PGC-1α protein content by Western blotting; GLUT4 and TNF-α gene expression by real-time polymerase chain reaction (PCR); and DNA methylation in the Slc2a4 gene promoter region by restriction digestion and real-time PCR. Analysis of variance was performed, followed by Tukey's post hoc test. p values <.05 were considered to be statistically significant. RESULTS: Maternal AP in four teeth decreased insulin-stimulated Akt serine and threonine phosphorylation status, reduced GLUT4 gene expression and its protein content, and increased NF-κB p50 and p65 subunits phosphorylation status in the GM of adult offspring. There were no alterations in the parameters analysed in the GM of adult offspring of rats with AP in a single tooth. In addition, maternal AP did not affect TNF-α gene expression and its protein content, PGC-1α protein content and DNA methylation in the Slc2a4 gene promoter region in the GM of adult offspring. CONCLUSIONS: Maternal AP in four teeth was associated with impairment in the final step of insulin signalling in the GM of adult male offspring in rats. An increase in NF-κB activity may be involved in this decrease in insulin signalling. This study demonstrates the impact of maternal AP on the health of offspring, demonstrating the importance of maintaining adequate maternal oral health to prevent diseases in adult offspring in rats.