The altered metabolic pathways of diffuse large B-cell lymphoma not otherwise specified.

Altered metabolic fingerprints of Diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS) may offer novel opportunities to identify new biomarkers and improve the understanding of its pathogenesis. This study aimed to investigate the modified metabolic pathways in extranodal, germinal center B-cell (GCB) and non-GCB DLBCL NOS from the head and neck. Formalin-fixed paraffin-embedded (FFPE) tissues from eleven DLBCL NOS classified according to Hans' algorithm using immunohistochemistry, and five normal lymphoid tissues (LT) were analyzed by high-performance liquid chromatography-mass spectrometry-based untargeted metabolomics. Partial Least Squares Discriminant Analysis showed that GCB and non-GCB DLBCL NOS have a distinct metabolomics profile, being the former more similar to normal lymphoid tissues. Metabolite pathway enrichment analysis indicated the following altered pathways: arachidonic acid, tyrosine, xenobiotics, vitamin E metabolism, and vitamin A. Our findings support that GCB and non-GCB DLBCL NOS has a distinct metabolomic profile, in which GCB possibly shares more metabolic similarities with LT than non-GCB DLBCL NOS.

Converting recycled membranes into photocatalytic membranes using greener TiO2-GRAPHENE oxide nanomaterials.

Despite the widespread use of membrane separation processes for water treatment, operation costs and fouling still restrict their application. Costs can be overcome by recycled membranes whereas fouling can be mitigated by membrane modification. In this work, the performance of recycled reverse osmosis membranes modified by greener titanium dioxide (TiO2) and graphene oxide (GO) in different modification routes were investigated and compared. The use of recycled membranes as a support acted more than a strategy for costs reduction, but also as an alternative for solid waste reduction. Low adhesion of nanoparticulate materials to the membrane surfaces were verified in depositions by self-assembly, whereas filtration and modification with dopamine generated membranes with well adhered and homogeneous layers. Considering the stability, permeability, and rejection efficiency of dyes as model substrates, the membranes modified with the aid of dopamine-TiO2-GO were the most promising. The nanomaterials increased the membrane hydrophilicity and formed a hydrated layer that repels the organic contaminants and reduces fouling. Besides membrane rejection, adsorption (contribution: ∼10%) and photocatalysis (contribution: ∼20%) were additional mechanisms for pollutants removal by the modified membranes. The photocatalytic membrane modified with dopamine-TiO2-GO was furthermore evaluated for the removal of six different pharmaceutical active compounds (PhACs), noticing gains in terms of removal efficiency (up to 95.7%) and fouling mitigation for the modified membrane compared to the original membranes. The photocatalytic activity still contributed to a simultaneous degradation of PhACs avoiding the generation of a concentrated stream for further disposal.

Integrated proteomics, phosphoproteomics and metabolomics analyses reveal similarities among giant cell granulomas of the jaws with different genetic mutations.

BACKGROUND: Giant cell granuloma of the jaws are benign osteolytic lesions of the jaws. These lesions are genetically characterized by mutually exclusive somatic mutations at TRPV4, KRAS, and FGFR1, and a fourth molecular subgroup which is wild-type for the three mutations. Irrespective of the molecular background, giant cell granulomas show MAPK/ERK activation. However, it remains unclear if these mutations lead to differences in their molecular signaling in giant cell granulomas. METHODS: Metabolomics, proteomics, and phosphoproteomics analyses were carried out in formalin-fixed paraffin-embedded samples of giant cell granuloma of the jaws. The study cohort consisted of five lesions harboring mutations in FGFR1, six in KRAS, five in TRPV4, and five that were wild-type for these mutations. RESULTS: Lesions harboring KRAS or FGFR1 mutations showed overall similar proteomics and metabolomics profiles. In all four groups, metabolic pathways showed similarity in apoptosis, cell signaling, gene expression, cell differentiation, and erythrocyte activity. Lesions harboring TRPV4 mutations showed a greater number of enriched pathways related to tissue architecture. On the other hand, the wild-type group presented increased number of enriched pathways related to protein metabolism compared to the other groups. CONCLUSION: Despite some minor differences, our results revealed an overall similar molecular profile among the groups with different mutational profile at the metabolic, proteic, and phosphopeptidic levels.

Biodegradability, environmental risk assessment and ecological footprint in wastewater technologies for pharmaceutically active compounds removal.

Several studies have investigated the removal of pharmaceutically active compounds (PhACs) by wastewater treatment technologies due to the risk that these compounds pose to the environment. In this sense, advanced biological processes have been developed for micropollutants removal, such as membrane bioreactors and moving bed biofilm reactors. Thus, this review holistically evaluated the biodegradation of 18 environmentally hazardous PhACs. Biological processes were assessed including removal efficiencies, environmental risk, and ecological footprint (consumption of resources and energy, atmospheric emissions, and waste generation). The maximum concentration of PhACs for a low or negligible risk scenario in treated wastewater and the potential of biological processes to meet this goal were assessed. Among the evaluated PhACs, the most biodegradable was paracetamol, while the most recalcitrant was diclofenac. Combination of conventional processes and advanced biological processes proved to be the most efficient way to remove several PhACs, mainly the osmotic membrane bioreactor.

Unveiling metabolic changes in marsupialized odontogenic keratocyst: A pilot study.

OBJECTIVE: We aimed to assess which metabolic pathways would be implicated in the phenotypic changes of the epithelial lining of odontogenic keratocyst after marsupialization, comparing pre- and post-marsupialized lesions with adjacent oral mucosa. MATERIALS AND METHODS: Eighteen formalin-fixed and paraffin-embedded tissues from six subjects were divided into three paired groups: odontogenic keratocyst pre- (n = 6) and post-marsupialization (n = 6), and adjacent oral mucosa (n = 6). The metabolic pathways found in these groups were obtained by high-performance liquid chromatography-mass spectrometry-based untargeted metabolomics performed. RESULTS: Through putative metabolite annotation followed by pathway enrichment and predictive analysis with automated algorithms (Mummichog and Gene Set Enrichment Analysis), we found differences in many cellular processes that may be involved in inflammation, oxidative stress response, keratinocyte-basal membrane attachment, differentiation, and proliferation functions, all relevant to odontogenic keratocyst pathobiology and the phenotype acquired after marsupialization. CONCLUSION: Our study was able to identify several metabolic pathways potentially involved in the metaplastic changes induced by marsupialization of odontogenic keratocysts. An improved comprehension of this process could pave the way for the development of targeted therapies.

Norfloxacin and gentamicin degradation catalyzed by manganese porphyrins under mild conditions: the importance of toxicity assessment.

The current work assessed the degradation degree and the degradation products derived from norfloxacin (NOR) and gentamicin (GEN) using iodosylbenzene and iodobenzene diacetate, in the presence of manganese porphyrin as catalysts. Better results for NOR degradation (> 80%) were obtained when more hydrophobic porphyrins were employed. ß-brominated manganese porphyrins showed a lower GEN degradation (~ 25%) than the non-brominated ones (~ 35%), probably due to their steric hindrance. In any case, complete mineralization was achieved neither for NOR nor for GEN, and the assignment of the generated products, complemented by the study of their toxicity, was an important step performed. From the obtained results, no correlation was found between the number of identified products and the reported toxicity value (rSpearman,NOR = 0.006; p value = 0.986 and rSpearman,GEN = - 0,198; p value = 0.583), which reinforces the idea of synergism and antagonistic phenomena. The higher degradation degree could have led to products of lower steric hindrance and easier penetration into the A. fischeri cells, which subsequently led to an increase in toxicity for these experiments. In most cases, the products presented higher toxicity than the original compound, which raises a concern about their occurrence in environmental matrices.

Influence of humic substances on the landfill leachate biodegradability with a focus on temporal seasonality.

The high resilience to biological treatments from the landfill leachate is generally associated with the presence of humic substances (HS). The brown color characteristic of this effluent is also related to these substances. Landfill leachate with low biodegradability can make biological treatments unfeasible, which can drive up the cost for the treatment of large leachate volumes. In this context, this research aimed to characterize the leachate in different seasonal periods, and verify the influence of HS species on the biodegradability of the effluent to assist in the selection of adequate treatment techniques. The HS quantification was performed using the modified Lowry method and speciation through fractionation according to the molar masses of the HS species. The tropical regions can be the precursor for the rapid stabilization of biodegradable organic matter. The warmer climate contributed to a reduced BOD/COD ratio (0.03) and the predominance of compounds of lower mass (e.g.: fulvic acids). The tests showed an HS concentration of 26.9% of the total COD in the raw leachate in the rainy season, which increased to 37.3% in the dry season. Approximately 70% of HS species refer to fulvic acids, a fraction identified as having the highest biologic treatment resilience.

Phenolic compounds in surface water: methodology and occurrence in Doce River, Brazil.

Phenolic compounds are widely spread in surface water, mainly in developing countries, where sewage and wastewater treatment are still reduced. Thus, this work quantified these pollutants in the Doce River analyzing the associated risk for the environment and human health. This river is in the state of Minas Gerais in Brazil and was recently impacted by the collapse of a mining dam that compromised the resilience of the entire watershed. For that purpose, a methodology for simultaneous identification and quantification of 17 different phenols was developed. It was possible to verify phenolic compounds' occurrence with concentration ranging from 0.13 to 24.16 µg·L-1. 2-Nitrophenol and bisphenol A appeared in all samples analyzed. The analytical method was processed using solid-phase extraction (SPE) (C18 cartridge), gas chromatography with FID, and mass spectrometry to define the analytes' retention time. For case validation, the selectivity, linearity, detection and quantification limits, sensitivity, precision, accuracy, resolution, matrix effect, and peak quality were assessed. Four different solvents were tested in the recovery-grade trials, which were dichloromethane, methanol, acetonitrile, and ethyl acetate. Among them, methanol had a better performance and was used throughout all analyses. The phenolic compounds had a recovery degree higher than 50% after SPE, regardless of the matrices.

A survey on experiences in leachate treatment: Common practices, differences worldwide and future perspectives.

The necessity for landfill leachate treatment is a requisite to reduce the environmental impact related to municipal solid waste landfills and different aspects must be considered while deciding for an appropriate treatment process. For example, it was demonstrated that the landfill leachate stabilization in tropical regions is achieved right after its first year of operation, requiring technologies capable of treating leachates of a higher recalcitrant character if compared to those leachates from temperate regions and same landfill age. In view of its complexity and variability, stand-alone processes (either biological or physicochemical) are often ineffective in attaining the threshold values for its discharge in receiving bodies. Due to that fact, full-scale facilities have adopted integrated routes, harvesting the benefits of both biological and physicochemical processes. The implementation of membrane bioreactors followed by polishing membrane separation process (nanofiltration and reverse osmosis) seems to be a trend in leachate treatment by full-scale treatment plants. This technology is widely employed in China, European countries, and tropical countries as Brazil, generally with a treatment cost lower than the costs related to its disposal in domestic effluent collection systems. From the technologies already employed by full-scale facilities, four integrated routes were proposed for a sensitive analysis considering the treatment of a landfill leachate of different physicochemical characteristics. From all routes, those employing the membrane separation process as a polishing step had a better efficacy in attaining the threshold values for leachate disposal, being that an interesting alternative for leachate polishing by full-scale facilities.

Age-Related Metabolic Pathways Changes in Dental Follicles: A Pilot Study.

Aging is not a matter of choice; it is our fate. The "time-dependent functional decline that affects most living organisms" is coupled with several alterations in cellular processes, such as cell senescence, epigenetic alterations, genomic instability, stem cell exhaustion, among others. Age-related morphological changes in dental follicles have been investigated for decades, mainly motivated by the fact that cysts and tumors may arise in association with unerupted and/or impacted teeth. The more we understand the physiology of dental follicles, the more we are able to contextualize biological events that can be associated with the occurrence of odontogenic lesions, whose incidence increases with age. Thus, our objective was to assess age-related changes in metabolic pathways of dental follicles associated with unerupted/impacted mandibular third molars from young and adult individuals. For this purpose, a convenience sample of formalin-fixed paraffin-embedded (FFPE) dental follicles from young (<16 y.o., n = 13) and adult (>26 y.o., n = 7) individuals was selected. Samples were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS)-based untargeted metabolomics. Multivariate and univariate analyses were conducted, and the prediction of altered pathways was performed by mummichog and Gene Set Enrichment Analysis (GSEA) approaches. Dental follicles from young and older individuals showed differences in pathways related to C21-steroid hormone biosynthesis, bile acid biosynthesis, galactose metabolism, androgen and estrogen biosynthesis, starch and sucrose metabolism, and lipoate metabolism. We conclude that metabolic pathways differences related to aging were observed between dental follicles from young and adult individuals. Our findings support that similar to other human tissues, dental follicles associated with unerupted tooth show alterations at a metabolic level with aging, which can pave the way for further studies on oral pathology, oral biology, and physiology.

Biosorption of methylene blue and eriochrome black T onto the brown macroalgae Fucus vesiculosus: equilibrium, kinetics, thermodynamics and optimization.

The present study had the objective to investigate the equilibrium, kinetics, thermodynamic viability and system optimization of methylene blue (MB) and eriochrome black T (ET) biosorption onto Fucus vesiculosus (F. vesiculosus). A comprehensive bioadsorbent characterization was carried out. The infrared spectra suggested a physical biosorption mechanism that was later proven by the enthalpy change and the isotherms models. Furthermore, the process was best described by Langmuir and Temkin isotherm models, indicating the monolayer formation and the linear reduction of the heat of biosorption with the coverage degree. F. vesiculosus presented a maximum biosorption capacity of 698.477 mg·g-1 for MB, and 24.306 mg·g-1 for ET. Regarding kinetics, the pseudo-second-order kinetic model was the best fitted model. In addition, the film diffusion was confirmed as the process limiting step. The model's optimization was achieved in order to maximize the removal efficiency, corresponding to 99.28% for MB and 99.44% for ET.

The environmental risks of pharmaceuticals beyond traditional toxic effects: Chemical differences that can repel or entrap aquatic organisms.

The aim of the present study was to assess the risks of four different pharmaceutical active compounds (PhACs; diazepam, metformin, omeprazole and simvastatin). Acute and chronic toxicities were studied using the bacterium Aliivibrio fischeri and the microalgae Pseudokirchneriella subcapitata; while the repellency and attractiveness were assessed by avoidance tests with juvenile Cypirinus carpio using a multi-compartmented exposure system. Omeprazole was found to be an acutely toxic drug (EC50: 0.015 mg/L), while the other PhACs, except simvastatin, showed some chronic toxicity. Regarding avoidance, simvastatin and omeprazole induced an escape response for 50% of the fish population at 0.032 and 0.144 mg/L, respectively; contrarily, diazepam was attractive, even at lethal concentrations, representing a dangerous trap for organisms. The toxicity of the PhACs seemed not to be directly related to their repellency; and the mode of action seems to determine the repellency or attractiveness of the chemicals. Contamination by PhACs is of concern due to the environmental disturbance they might cause, either due to their acute and chronic toxicity (at the individual level), repellency (at the ecosystem level: loss of local biodiversity) or attraction to potentially lethal levels.

Occurrence and risk assessment of pharmaceutically active compounds in water supply systems in Brazil.

The presence of pharmaceutically active compounds (PhACs) in water supply systems has been generating great concern about their effects on the environment and human health. Twenty-eight PhACs were monitored during one year in four Brazilian water sources, aiming to understand the factors that influence their occurrence and removal in conventional drinking water treatment plants (DWTPs) and to assess the environmental and human health risks. Trace levels of PhACs were detected in surface and drinking water in all assessed water sources. Effects of seasonality and socioeconomic aspects were observed in PhACs occurrence, like their higher concentrations during winter and in locales with higher values of gross domestic product per capita and human development index. Betamethasone, prednisone, and fluconazole were the most commonly detected PhACs, and also presented the highest concentrations. However, they were not related to toxicological risks. Nonetheless, all surface waters were subject to toxicological risk owing to at least one PhAC. PhACs related to the highest toxicological risks were loratadine, atorvastatin, norfloxacin, caffeine, and ranitidine, however, all these PhACs presented low quantification frequency. DWTPs capacity to remove PhACs was only partial, so treated water was still contaminated with these compounds. Furthermore, atorvastatin presented a margin of exposure below 100, indicating possible risk for public health. Thus, additional advanced treatment steps should be considered to improve PhACs removal during drinking water treatment.

Diazepam, metformin, omeprazole and simvastatin: a full discussion of individual and mixture acute toxicity.

High consumption of drugs, combined with their presence in the environment, raises concerns about its consequences. Even though researches are often engaged in analyzing substances separately, that is not the environmental reality. Therefore, the aim of this study was to investigate the acute toxicity of the pharmaceuticals simvastatin, metformin, omeprazole and diazepam, and all possible mixtures between them, to the organism Aliivibrio fischeri, verifying possible synergistic or antagonistic effects and assessing byproducts formation. In terms of individual toxicity, omeprazole is the most toxic of the active ingredients, followed by simvastatin, diazepam and, finally, metformin. When the toxicity of mixtures was tested, synergism, antagonism and hormesis were perceived, most probably generated due to byproducts formation. Moreover, it was observed that even when compounds are at concentrations below the non-observed effect concentration (NOEC), there may be toxicity to the mixture. Hence, this work points to the urgent need for more studies involving mixtures, since chemicals are subject to interactions and modifications, can mix, and potentiate or nullify the toxic effect of each other.

Graphene oxide in the remediation of norfloxacin from aqueous matrix: simultaneous adsorption and degradation process.

In the present study, the simultaneous adsorption degradation of norfloxacin (NOR) by graphene oxide from aqueous matrix was verified. Graphene oxide (GO, ~ 8 layers) was prepared using modified Hummers method through the oxidation/exfoliation of expanded graphite. Spectroscopic techniques confirmed the NOR adsorption onto GO surface and the partial antibiotic degradation promoted by hydroxyl radicals derived from GO. Furthermore, the mass spectra after the adsorption-degradation processes showed NOR degradation intermediates that was compared and confirmed by other studies. The nanomaterial showed a removal capacity of 374.9 ± 29.8 mg g-1, observing greater contribution from the NOR in the zwitterionic form and removals up to 94.8%. The intraparticle diffusion process, assessed by Boyd's model and Fick's law, presented a greater contribution in the removal process, reaching the equilibrium 30 min after the beginning. In addition, the temperature increase would disadvantage the process, which was considered thermodynamically viable throughout the evaluated temperature range. Finally, the process was scaled-up in a single stage batch adsorber considering a NOR removal efficiency of 95%. This resulted in mass requirement of 63.6 g of GO in order to treat 0.5 m3 of contaminated water. In general, the simultaneous adsorption-degradation process was considered innovative and promising in pharmaceutical compounds remediation.

Estudo da biodegradabilidade de fluoroquinolona por meio da utilização de biomassas aeróbias e anaeróbias / Study of fluoroquinolone biodegradability by using aerobic and anaerobic biomass

RESUMO Os antibióticos como o norfloxacino constituem os fármacos mais utilizados na Medicina, com consumos expressivos no mundo todo. Por ser quimicamente estável, após sua administração a maior parte do fármaco é excretada de forma inalterada e, geralmente, é removida apenas parcialmente nas estações de tratamento de esgoto (ETEs). Assim, o presente trabalho buscou avaliar a eficiência dos processos biológicos na remediação de norfloxacino investigando os mecanismos de remoção envolvidos. O objetivo foi verificar a biodegradabilidade do fármaco e sua toxicidade. Para realização dos ensaios de biodegradabilidade, coletaram-se lodos na ETE Arrudas (Sabará, Minas Gerais) dos processos de tratamento com lodos ativados, reatores upflow anaerobic sludge blanket (UASB) e biodigestor anaeróbio. Reatores em escala de bancada foram montados com lodo aclimatado e não aclimatado. Amostras tiveram a biodegradabilidade acompanhada por meio da determinação do carbono orgânico total e da absortividade molar do norfloxacino por espectrofotometria de UV/Vis. Determinou-se a toxicidade por intermédio de ensaios com a bactéria Aliivibrio fischeri. Entre as biomassas utilizadas, a mais eficiente na remoção do norfloxacino foi advinda dos reatores UASB (23%), seguida do biodigestor anaeróbio (18%) e, então, dos lodos ativados (13%). Quanto à ecotoxicidade, a degradação anaeróbia promoveu a eliminação da toxicidade do antibiótico, enquanto com relação à degradação aeróbia os efluentes gerados permanecem tóxicos.

ABSTRACT Antibiotics, such as norfloxacin, are the most widely used drugs in medicine, with significant consumption in the world. By being chemically stable, most of the drug is excreted unchanged after administration, and is generally only partially removed in the sewage treatment plants (STPs). Thus, the efficiency of biological processes in the remediation of norfloxacin was investigated by the present work, verifying the removal mechanisms involved. Its objective was to verify the drug's biodegradability and toxicity. In order to perform biodegradability tests, sludges were collected in Arrudas STP (Sabara, Minas Gerais) from the treatment processes with activated sludge, upflow anaerobic sludge blanket (UASB) reactors and anaerobic biodigester. Bench-scale reactors were assembled with acclimatized and non-acclimatized sludge. Samples had their biodegradability monitored by determination of total organic carbon and norfloxacin molar absorptivity by UV/Vis spectrophotometry. The toxicity was determined by tests with Aliivibrio fischeri. Among the used biomass, UASB reactors was the most efficient in removing norfloxacin (23%), followed by anaerobic biodigester (18%), and activated sludge (13%). Regarding ecotoxicity, the anaerobic degradation promoted the elimination of antibiotic toxicity, while with aerobic degradation, the effluents generated remained toxic.