CD73 mitigates ZEB1 expression in papillary thyroid carcinoma.

BACKGROUND: ZEB1, a core transcription factor involved in epithelial-mesenchymal transition (EMT), is associated with aggressive cancer cell behavior, treatment resistance, and poor prognosis across various tumor types. Similarly, the expression and activity of CD73, an ectonucleotidase implicated in adenosine generation, is an important marker of tumor malignancy. Growing evidence suggests that EMT and the adenosinergic pathway are intricately linked and play a pivotal role in cancer development. Therefore, this study focuses on exploring the correlations between CD73 and ZEB1, considering their impact on tumor progression. METHODS: We employed CRISPR/Cas9 technology to silence CD73 expression in cell lines derived from papillary thyroid carcinoma. These same cells underwent lentiviral transduction of a reporter of ZEB1 non-coding RNA regulation. We conducted studies on cell migration using scratch assays and analyses of cellular speed and polarity. Additionally, we examined ZEB1 reporter expression through flow cytometry and immunocytochemistry, complemented by Western blot analysis for protein quantification. For further insights, we applied gene signatures representing different EMT states in an RNA-seq expression analysis of papillary thyroid carcinoma samples from The Cancer Genome Atlas. RESULTS: Silencing CD73 expression led to a reduction in ZEB1 non-coding RNA regulation reporter expression in a papillary thyroid carcinoma-derived cell line. Additionally, it also mitigated ZEB1 protein expression. Moreover, the expression of CD73 and ZEB1 was correlated with alterations in cell morphology characteristics crucial for cell migration, promoting an increase in cell polarity index and cell migration speed. RNA-seq analysis revealed higher expression of NT5E (CD73) in samples with BRAF mutations, accompanied by a prevalence of partial-EMT/hybrid state signature expression. CONCLUSIONS: Collectively, our findings suggest an association between CD73 expression and/or activity and the post-transcriptional regulation of ZEB1 by non-coding RNA, indicating a reduction in its absence. Further investigations are warranted to elucidate the relationship between CD73 and ZEB1, with the potential for targeting them as therapeutic alternatives for cancer treatment in the near future.

Hospitalizations for Cardiovascular Diseases Sensitive to Primary Health Care in Paraná State, Brazil: A Bayesian Spatiotemporal Model.

PURPOSE: To analyze spatiotemporal trends in hospitalizations for cardiovascular diseases (CVD) sensitive to primary health care (PHC) among individuals aged 50-69 years in Paraná State, Brazil, from 2014 to 2019 and investigate correlations between PHC services and the Social Development Index. METHODS: We conducted a cross-sectional ecological study using publicly available secondary data to analyze the municipal incidence of hospitalizations for CVD sensitive to PHC and to estimate the risk of hospitalization for this group of diseases and associated factors using hierarchical Bayesian spatiotemporal modeling with Markov chain Monte Carlo simulation. RESULTS: There was a 5% decrease in the average rate of hospitalizations for PHC-sensitive CVD from 2014 to 2019. Regarding standardized hospitalization rate (SHR) according to population size, we found that no large municipality had an SHR >2. Likewise, a minority of these municipalities had SHR values of 1-2 (33%). However, many small and medium-sized municipalities had SHR values >2 (47% and 48%, respectively). A greater Social Development Index value served as a protective factor against hospitalizations, with a relative risk of 0.957 (95% credible interval, 0.929-0.984). CONCLUSIONS: The annual risk of hospitalization decreased over time; however, small municipalities had the greatest rates of hospitalization, indicating an increase in health inequity. The inverse association between social development and hospitalizations for CVD sensitive to PHC raises questions about intersectionality in health care.

Racial inequalities in the development of multimorbidity of chronic conditions: results from a Brazilian prospective cohort.

BACKGROUND: The occurrence of multimorbidity and its impacts have differentially affected population subgroups. Evidence on its incidence has mainly come from high-income regions, with limited exploration of racial disparities. This study investigated the association between racial groups and the development of multimorbidity and chronic conditions in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS: Data from self-reported white, brown (pardos or mixed-race), and black participants at baseline of ELSA-Brasil (2008-2010) who were at risk for multimorbidity were analysed. The development of chronic conditions was assessed through in-person visits and self-reported diagnosis via telephone until the third follow-up visit (2017-2019). Multimorbidity was defined when, at the follow-up visit, the participant had two or more morbidities. Cumulative incidences, incidence rates, and adjusted incidence rate ratios (IRRs) were estimated using Poisson models. RESULTS: Over an 8.3-year follow-up, compared to white participants: browns had a 27% greater incidence of hypertension and obesity; and blacks had a 62% and 45% greater incidence, respectively. Blacks also had 58% more diabetes. The cancer incidence was greater among whites. Multimorbidity affected 41% of the participants, with a crude incidence rate of 57.5 cases per 1000 person-years (ranging from 56.3 for whites to 63.9 for blacks). Adjusted estimates showed a 20% higher incidence of multimorbidity in black participants compared to white participants (IRR: 1.20; 95% CI: 1.05-1.38). CONCLUSIONS: Significant racial disparities in the risk of chronic conditions and multimorbidity were observed. Many associations revealed a gradient increase in illness risk according to darker skin tones. Addressing fundamental causes such as racism and racial discrimination, alongside considering social determinants of health, is vital for comprehensive multimorbidity care. Intersectoral, equitable policies are essential for ensuring health rights for historically marginalized groups.

Prevalence, incidence, risk factors and residual risk associated with viral infections among eligible Brazilian blood donors.

Knowledge regarding the profile of eligible blood donors presenting positive results in laboratory screening is essential for reducing transfusion-transmitted human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). Our study aimed to evaluate the prevalence, incidence, predictor variables and residual risk (RR) of HIV/HBV/HCV in blood bags donated in Minas Gerais, Brazil. This study analysed data retrieved from the records of a large blood bank relating to donations collected at multiple centres within the period 2012-2018, during which 1 991 120 blood bags were screened using immunoassays and nucleic acid tests (NATs). Multilevel modelling was used to investigate the association between sex, civil status and age group with HIV/HBV/HCV. RR was estimated from the incidence values (restricted to negative and positive tests within the study period) and window periods for infections. The prevalence in first time donors, incidence and RR of HCV (223.73 cases per 100 000; 54.84 per 100 000 persons-year and 1.6527 per 100 000, respectively) were higher than those of HIV (172.65 cases per 100 000; 28.25 per 100 000 persons-year and 0.8514 per 100 000) and HBV (168.17 cases per 100 000; 18.54 per 100 000 persons-year and 0.5588 per 100 000). The odds of acquiring infection were greater in male, single and older donors. Sixteen donors were identified as seronegative and NATs+ during the 7-year span of the study. Our study has clarified some spatiotemporal trends regarding HIV/HBV/HCV infections in donated blood in Brazil. The results will contribute to the formulation of directives addressed to high-risk donors.

Human cystic echinococcosis: first molecular identification of Echinococcus canadensis G7 in Brazil.

Echinococcus granulosus sensu lato (s.l.) is a species complex with the potential to cause cystic echinococcosis (CE). Contact with the feces of domestic dogs (Canis familiaris) fed with raw viscera of intermediate livestock hosts is a risk factor for this infection in the southern region of Brazil. Although the region has been considered endemic to CE for many years, molecular data regarding the species of the complex causing CE in humans are scarce. This study aimed to perform a molecular analysis of the biological fluid from a human liver cyst to investigate the species responsible for CE. Genetic material obtained from the hydatid fluid of a hepatic cyst from a human with CE was subjected to PCR to amplify mitochondrial and nuclear DNA sequences. The phylogenetic analysis confirmed the human infection by Echinococcus canadensis G7 in the state of Paraná, Brazil. This is the first molecular record of E. canadensis G7 infecting a human in Brazil, and it is important to reiterate the risk of human CE caused by this species in South America, as reported by a previous study in Patagonia, Argentina. From the epidemiological point of view, this finding is of great relevance for the southern region of Brazil, since this parasite has previously only been detected in pigs in the state of Rio Grande do Sul, neighboring Paraná. The finding points to the importance of this identification in the molecular epidemiology of E. granulosus s.l., especially in South America.

Abundance of the bat Sturnira lilium (Phyllostomidae) in relation Solanum mauritianum (Solanaceae) diaspores in an Atlantic Forest fragment of southern Brazil.

Frugivore bats are important seed dispersers in forests and their abundance are associated with the presence of zoochoric plants. In this context, the aim of our study was to investigate the association of the frugivore bat S. lilium with the diaspores of the zoochoric plant S. mauritianum, a common arboreal species present in forest fragments of southern Brazil. We also investigated the diet of the species based on seed content present in feces of individuals. Bats were mist-netted from November 2017 to April 2018 in a fragment of Atlantic Forest. The proportion of immature and mature diaspores of S. mauritianum was estimated in the same area where bats were sampled, and feces were sampled from captured individuals. In total, 61 individuals of S. lilium were captured, and 795 seeds were sampled from their feces. The abundance of S. lilium was significantly associated with the proportion of immature diaspores of S. mauritianum. We identified seeds of two botanical families: Solanaceae (89%) and Moraceae (11%) in the fecal samples. Our findings support the view that S. lilium is a legitimate disperser of S. mauritianum, and that its ecological function is probably a result of co-adaptation.

Exercise improves respiratory function, body fluid and nitric oxide in hemodialysis patients.

Emerging evidence suggests that resistance training (RT) can mitigate respiratory muscle weakness in hemodialysis (HD) patients. However, the underlying mechanisms responsible for these beneficial effects remain unclear. The purpose of this study was to assess the impact of periodized RT on respiratory muscle strength and its relationship with handgrip strength (HGS), fat-free mass (FFM), nitric oxide (NO), and interdialytic weight gain (IWG) in HD patients. Thirty-three patients were randomly assigned to two groups: control (CTL; n=18) and RT (n=15). RT group did not perform any additional exercise training specific to the respiratory tract. Maximal inspiratory (MIP) and expiratory (MEP) pressures, peak expiratory flow (PEF), HGS, FFM, NO, and IWG were measured before and after the intervention period. Participants in the RT group engaged in a 24-week RT program, three times per week. RT resulted in significant improvements in MIP, MEP, PEF, as well as enhancements in HGS, FFM, NO, and IWG (p<0.05). Notably, inverse correlations were observed between MIP (r= -0.37, p=0.03) and PEF (r= -0.4, p=0.02) with IWG. Thus, the amelioration of HGS and FFM coincided with a reduction in respiratory muscle weakness among HD patients. Decreased IWG and increased circulating NO are plausible mechanisms contributing to these improvements.

A Proposal for a Solar Position Sensor System with Multifiber Optical Cable.

A solar position sensor is an essential optoelectronic device used to monitor the sun's position in solar tracking systems. In closed-loop systems, this sensor is responsible for providing feedback signals to the control system, allowing motor adjustments to optimize the angle of incidence and minimize positioning errors. The accuracy required for solar tracking systems varies depending on the specific photovoltaic concentration. In the case of the concentrator photovoltaic (CPV), it is normally essential to track the sun with a position error of less than ±0.6°. To achieve such precision, a proposed sensor configuration composed of low-cost embedded electronics and multifiber optical cable is subjected to characterization through a series of measurements covering range, sensitivity, and resolution. These measurements are performed in controlled indoor environments as well as outdoor conditions. The results obtained exhibit a resolution of 2.6×10-3 degrees when the sensor is illuminated within its designated field of view of ±0.1°, particularly in external conditions. Considering the performance demonstrated by the proposed solar position sensor, coupled with its straightforward modeling and assembly compared to position sensors documented in the literature, it emerges as a promising candidate for integration into solar tracking systems.

The crossroads of adenosinergic pathway and epithelial-mesenchymal plasticity in cancer.

Epithelial-mesenchymal transition (EMT) is a key mechanism related to tumor progression, invasion, metastasis, resistance to therapy and poor prognosis in several types of cancer. However, targeting EMT or partial-EMT, as well as the molecules involved in this process, has remained a challenge. Recently, the CD73 enzyme, which hydrolyzes AMP to produce adenosine (ADO), has been linked to the EMT process. This relationship is not only due to the production of the immunosuppressant ADO but also to its role as a receptor for extracellular matrix proteins, being involved in cell adhesion and migration. This article reviews the crosstalk between the adenosinergic pathway and the EMT program and the impact of this interrelation on cancer development and progression. An in silico analysis of RNAseq datasets showed that several tumor types have a significant correlation between an EMT score and NT5E (CD73) and ENTPD1 (CD39) expressions, with the strongest correlations being in prostate adenocarcinoma. Furthermore, it is evident that the cooperation between EMT and the adenosinergic pathway in tumor progression is context and tumor-dependent. The increased knowledge about this topic will help broaden the view to explore new treatments and therapies for different types of cancer.

Dysfunctional phenotype of systemic and pulmonary regulatory T cells associate with lethal COVID-19 cases.

Severe cases of COVID-19 present hyperinflammatory condition that can be fatal. Little is known about the role of regulatory responses in SARS-CoV-2 infection. In this study, we evaluated the phenotype of regulatory T cells in the blood (peripheral blood mononuclear cell) and the lungs (broncho-alveolar) of adult patients with severe COVID-19 under invasive mechanical ventilation. Our results show important dynamic variation on Treg cells phenotype during COVID-19 with changes in number and functional parameters from the day of intubation (Day 1 of intensive care unit admission) to Day 7. We observed that compared with surviving patients, non-survivors presented lower numbers of Treg cells in the blood. In addition, lung Tregs of non-survivors also displayed higher PD1 and lower FOXP3 expressions suggesting dysfunctional phenotype. Further signs of Treg dysregulation were observed in non-survivors such as limited production of IL-10 in the lungs and higher production of IL-17A in the blood and in the lungs, which were associated with increased PD1 expression. These findings were also associated with lower pulmonary levels of Treg-stimulating factors like TNF and IL-2. Tregs in the blood and lungs are profoundly dysfunctional in non-surviving COVID-19 patients.

Role of the iNOS isoform in the cardiovascular dysfunctions of male rats with 6-OHDA-induced Parkinsonism.

INTRODUCTION: Available studies have shown the involvement of nitric oxide (NO) in the processes that lead to neurodegeneration in Parkinson's disease (PD). Also, the use of inhibitors of the inducible isoform of NO-synthase (iNOS) promotes neuroprotection and attenuates dopamine (DA) loss in experimental models of Parkinsonism. In addition, NO also appears to be involved in cardiovascular changes in 6-hydroxydopamine (6-OHDA)-induced Parkinsonism. The current study aimed to evaluate the effects of iNOS inhibition on cardiovascular and autonomic function in animals that were subjected to Parkinsonism by the administration of 6-OHDA. MATERIALS AND METHODS: The animals underwent stereotaxic surgery for bilateral microinfusion of the neurotoxin 6-OHDA (6 mg/mL in 0.2% ascorbic acid in sterile saline solution) or vehicle solution for the Sham group. From the day of stereotaxis until the day of femoral artery catheterization, the animals were treated with the iNOS inhibitor, S-methylisothiourea (SMT; 10 mg/kg; i. p.) or saline solution (0.9%; i. p.) for 7 days. The animals were divided into four groups: Sham-Saline, Sham-SMT, 6-OHDA-Saline, and 6-OHDA-SMT. Subsequent analyses were performed on these four groups. After 6 days, they underwent catheterization of the femoral artery, and 24 h later, mean arterial pressure (MAP) and heart rate (HR) were recorded. Another group of animals (the 6-OHDA and Sham groups) was assessed for aortic vascular reactivity after 7 days of bilateral infusion of 6-OHDA or vehicle, in which cumulative concentration-effect curves (CCEC) were made for phenylephrine (Phenyl), acetylcholine and sodium nitroprusside (NPS). Also, CCEC in the presence of Nw-nitro-arginine-methyl-ester (l-NAME) (10-5 M), SMT (10-6 M), and indomethacin (10-5 M) blockers were made. RESULTS: The effectiveness of the 6-OHDA lesion was confirmed with the reduction of DA in 6-OHDA animals. However, treatment with SMT could not reverse the loss of DA. Concerning the baseline parameters, SBP and MAP values were lower in 6-OHDA animals compared to their Sham control, with no effect of treatment with SMT. In the analysis of SBP variability, a decrease in variance, the VLFabs component, and the LFabs component were observed in the 6-OHDA groups when compared to their controls, regardless of treatment with SMT. It was also observed that intravenous injections of SMT resulted in an increase in BP and a decrease in HR. However, the response was not different between the Sham and 6-OHDA groups. In vascular function, there was a hyporeactivity to Phenyl in the 6-OHDA group, and when investigating the mechanisms of this hyporeactivity, it was seen that the Rmax to Phenyl increased with incubation with SMT, indicating that iNOS could be involved in the vascular hyporeactivity of animals with Parkinsonism. CONCLUSION: Thus, the set of results presented in this study suggests that part of the cardiovascular dysfunction in animals subjected to 6-OHDA Parkinsonism may be peripheral and involve the participation of endothelial iNOS.

Reduction in the number of neutrophils in the broncho-alveolar aspirate is associated with worse prognosis in elderly patients with severe COVID-19.

The blood levels of neutrophils are associated with the severity of COVID -19. However, their role in the pulmonary environment during COVID -19 severity is not clear. Here, we found a decrease in the neutrophil count in BAL (bronchoalveolar lavage) in non-survivors and in older patients (> 60 years). In addition, we have shown that older patients have higher serum concentration of CXCL8 and increased IL-10 expression by neutrophils.

High prevalence of central nervous system cryptococcosis using a fingerprick whole-blood lateral flow assay in individuals with neurological symptoms and advanced HIV disease in a Brazilian emergency department.

Timely diagnosis is key in managing central nervous system (CNS) cryptococcosis in people living with HIV/AIDS (PLWHA). There are few data on implementing fingerprick whole-blood cryptococcal antigen (CrAg) lateral flow assay (LFA) as the first test for diagnosing CNS cryptococcosis. We evaluated the prevalence of CNS cryptococcosis and cryptococcal antigenemia using fingerprick whole-blood in a referral emergency department (ED) in São Paulo, Brazil. This was a prospective cohort study of consecutive adult PLWHA with advanced HIV disease and neurological symptoms. Fingerprick whole-blood CrAg LFA was performed at bedside. Seventy-four individuals were enrolled (median age = 40 years; males = 62%). Prevalence of CNS cryptococcosis was 17.6% (13/74); 95% confidence interval (CI), 9.4-30.0%, and prevalence of positive fingerprick whole-blood CrAg LFA was 25.7% (19/74); 95% CI, 15.5-40.1%. Among the six (8.1%) patients with positive fingerprick whole-blood CrAg LFA and negative CSF CrAg LFA, four (5.4%) had isolated asymptomatic cryptococcal antigenemia, one (1.3%) had symptomatic cryptococcal antigenemia, and one (1.3%) had cryptococcemia. Prevalence of CNS cryptococcosis and cryptococcal antigenemia using fingerprick whole-blood CrAg LFA was high. Point-of-care testing was important for diagnosing CNS cryptococcosis in an ED from a middle-income country.

Diet supplementation with egg yolk powder fattens the beetle Tribolium castaneum.

Insects have become essential models in studying human metabolic diseases, mainly due to their low maintenance cost and available tools. Both mutations and modified diets induce metabolic states similar to human obesity and diabetes. Here, we explore the effect of a high-calorie, high-fat diet on the metabolism of the beetle Tribolium castaneum. Supplementation of the wheat flour diet with powdered egg yolk for 3 weeks increased the total triacylglycerol and accelerated larval development. In addition, this diet increased the triacylglycerol levels of adult beetles. However, this egg yolk supplementation did not alter the larvae's total glucose levels or lipogenic capacity and ATP citrate lyase activity. The diet also did not change the expression profile of several lipid and carbohydrate metabolism genes and insulin-like peptides. Thus, we conclude that the diet supplemented with egg yolk induces increased fat without causing diabetes phenotypes, as seen in other hypercaloric diets in insects.

Red biocolorant from endophytic Talaromyces minnesotensis: production, properties, and potential applications.

Fungal colorants are gradually entering the global color market, given their advantages of being less harmful to human health, as well as having greater stability and biotechnological potential, compared to other natural sources. The present work concerns the isolation and identification of an endophytic filamentous fungus, together with the chemical characterization and assessment of the fluorescence, toxicity, stability, and application potential of its synthesized red colorant. The endophytic fungus was isolated from Hymenaea courbaril, a tree from the Brazilian savannah, and was identified as Talaromyces minnesotensis by phenotypic and genotypic characterization. Submerged cultivation of the fungus resulted in the production of approximately 12 AU500 of a red biocolorant which according to LC-DAD-MS analysis is characterized by being a complex mixture of molecules of the azaphilone class. Regarding cytotoxicity assays, activity against human hepatoblastoma (HepG2) cells was only observed at concentrations above 5.0 g L-1, while antimicrobial effects against pathogenic bacteria and yeast occurred at concentrations above 50.0 g L-1. The biocolorant showed high stability at neutral pH values and low temperatures (10 to 20 °C) and high half-life values (t1/2), which indicates potential versatility for application in different matrices, as observed in tests using detergent, gelatin, enamel, paint, and fabrics. The results demonstrated that the biocolorant synthesized by Talaromyces minnesotensis has potential for future biotechnological applications. KEY POINTS: • An endophytic fungus, which was isolated and identified, synthesize a red colorant. • The colorant showed fluorescence property, low toxicity, and application potential. • The red biocolorant was highly stable at pH 8.0 and temperatures below 20°C.

Metabarcoding approach to identify bacterial community profiling related to nosocomial infection and bacterial trafficking-routes in hospital environments.

Nosocomial infections (NIs) appear in patients under medical care in the hospital. The surveillance of the bacterial communities employing high-resolution 16S rRNA profiling, known as metabarcoding, represents a reliable method to establish factors that may influence the composition of the bacterial population during NIs. The present study aimed to utilize high-resolution 16S rRNA profiling to identify high bacterial diversity by analyzing 11 inside and 10 outside environments from the General Hospital of Ribeirão Preto Medical School, Brazil. Our results identified a high bacterial diversity, and among these, the most abundant bacterial genera linked to NIs were Cutibacterium, Streptococcus, Staphylococcus, and Corynebacterium. A Acinetobacter was detected in cafeterias, bus stops, and adult and pediatric intensive care units (ICUs). Data suggest an association between transport and alimentation areas proximal to the hospital ICU environment. Interestingly, the correlation and clusterization analysis showed the potential of the external areas to directly influence the ICU pediatric department microbial community, including the outpatient's clinic, visitor halls, patient reception, and the closest cafeterias. Our results demonstrate that high-resolution 16S rRNA profiling is a robust and reliable tool for bacterial genomic surveillance. In addition, the metabarcoding approach might help elaborate decontamination policies, and consequently reduce NIs.

A look through Latin America truck drivers' health, a systematic review and meta-analysis.

Heavy truck drivers represent a social group of great importance to any country's economy. Their professional activity requires a high level of dedication. Due to the irregular hours in their work routine and adopted habits, they mostly predispose them to a diversity of health problems. The purpose of this study is to perform a systematic review and meta-analysis aiming to identify the prevalence of diabetes, hypertension, and obesity in Latin American Truck Drivers. We searched the PubMed, Web of Science, Scopus and LILACS databases, for scientific publications articles, as reported by The PRISMA Statement. From 1,382, 7 studies were included according to the established criteria. The hypertension prevalence found was 34.2%, diabetes was of 9.2% and the highest prevalence found was for overweight and obesity (56%). Meta-analysis presented that drivers have a higher prevalence of overweight or obesity when compared to eutrophic individuals and that drivers with diabetes and hyperglycemia have a lower prevalence. Due to their work activity, their access to the health system is compromised limiting any type of monitoring of their health. This study showed that there is, in Latin America, an investment and assistance gap, both in the health sector and in the research section, for this professional category, which is so important to the economy of these countries. These data should help to identify the difficulties faced by this professional in health assistance, road safety, public safety, leisure and social life. This research also highlighted that they are young and already have the first sign of non-transmissible chronic diseases, which is overweight and obesity.

Assessment of artificial neural networks to predict red colorant production by Talaromyces amestolkiae.

Consumer choice is typically influenced by color, leading to an increase in the use of artificial colorants by industry. However, several artificial colorants have been banned due to their harmful effects on human health and the environment, leading to increased interest in colorants from natural sources. Natural colorants can be found in plants, insects, and microorganisms. The importance of evaluating the technical and cost feasibility for the production of natural colorants are important factors for the replacement of artificial counterpart. Therefore, it is highly beneficial to predict the productivity of microbial colorants. The use of statistical methods that generate polynomial models through multiple regressions can provide information of interest about a bioprocess. However, modeling and control of biological processes require complex systems models, because they are nonlinear and non-deterministic systems. In this regard, artificial neural networks are suitable for estimating bioprocess variables with systems modeling. In this work, two different strategies were developed to predict the production of red colorants by Talaromyces amestolkiae, namely simulation by artificial neural networks (ANN) and response surface methodology (RSM). The results showed that the colorant concentration predicted by ANN is closer to the experimental data than that predicted by polynomial models fitted by multiple regression. Thus, this work suggests that the use of ANN can identify the initial conditions of the culture parameters that have the greatest influence on colorant production and can be a tool to be employed to improve the production of biotechnological products, such as microbial colorants.

Heating Capacity and Biocompatibility of Hybrid Nanoparticles for Magnetic Hyperthermia Treatment.

Cancer is one of the deadliest diseases worldwide and has been responsible for millions of deaths. However, developing a satisfactory smart multifunctional material combining different strategies to kill cancer cells poses a challenge. This work aims at filling this gap by developing a composite material for cancer treatment through hyperthermia and drug release. With this purpose, magnetic nanoparticles were coated with a polymer matrix consisting of poly (L-co-D,L lactic acid-co-trimethylene carbonate) and a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer. High-resolution transmission electron microscopy and selected area electron diffraction confirmed magnetite to be the only iron oxide in the sample. Cytotoxicity and heat release assays on the hybrid nanoparticles were performed here for the first time. The heat induction results indicate that these new magnetic hybrid nanoparticles are capable of increasing the temperature by more than 5 °C, the minimal temperature rise required for being effectively used in hyperthermia treatments. The biocompatibility assays conducted under different concentrations, in the presence and in the absence of an external alternating current magnetic field, did not reveal any cytotoxicity. Therefore, the overall results indicate that the investigated hybrid nanoparticles have a great potential to be used as carrier systems for cancer treatment by hyperthermia.

Specialized Pro-Resolving Lipid Mediators: Endogenous Roles and Pharmacological Activities in Infections.

During an infection, inflammation mobilizes immune cells to eliminate the pathogen and protect the host. However, inflammation can be detrimental when exacerbated and/or chronic. The resolution phase of the inflammatory process is actively orchestrated by the specialized pro-resolving lipid mediators (SPMs), generated from omega-3 and -6 polyunsaturated fatty acids (PUFAs) that bind to different G-protein coupled receptors to exert their activity. As immunoresolvents, SPMs regulate the influx of leukocytes to the inflammatory site, reduce cytokine and chemokine levels, promote bacterial clearance, inhibit the export of viral transcripts, enhance efferocytosis, stimulate tissue healing, and lower antibiotic requirements. Metabolomic studies have evaluated SPM levels in patients and animals during infection, and temporal regulation of SPMs seems to be essential to properly coordinate a response against the microorganism. In this review, we summarize the current knowledge on SPM biosynthesis and classifications, endogenous production profiles and their effects in animal models of bacterial, viral and parasitic infections.