The role of genetic polymorphisms for inducing genotoxicity in workers occupationally exposed to benzene: a systematic review.

Benzene is used worldwide as a major raw material in a number of industrial processes and also a potent airborne pollutant emitted from traffic exhaust fume. The present systematic review aimed to identify potential associations between genetic polymorphisms and occupational benzene-induced genotoxicity. For this purpose, a total of 22 selected studies were carefully analysed. Our results revealed a positive relation between gene polymorphism and genotoxicity in individuals exposed to benzene, since 17 studies (out of 22) observed positive relations between genotoxicity and polymorphisms in xenobiotics metabolizing genes influencing, therefore, individuals' susceptibility to genomic damage induced by benzene. In other words, individuals with some genotypes may show increase or decrease DNA damage and/or higher or lower DNA-repair potential. As for the quality assessment, 17 studies (out of 22) were categorized as Strong or Moderate and, therefore, we consider our findings to be trustworthy. Taken together, such findings are consistent with the notion that benzene induces genotoxicity in mammalian cells being strongly dependent on the genetic polymorphism. Certainly, such findings are important for clarifying the role of biomarkers related to genotoxicity in human biomonitoring studies.

Assessing the rigidity of cubanes and bicyclo(1.1.1)pentanes as benzene bioisosteres.

Aromatic rings are critical core substructures in the majority of pharmaceutical compounds. There is much recent interest in replacing aromatic structures with saturated bioisosteres of benzene, which are generally fused or bridged ring systems. These bioisosteres often show improved solubility properties compared to benzene, and may also undergo fewer unwanted metabolic processes. One key reason why aromatic rings have proven so successful in drug design is their rigidity. This paper uses molecular dynamics simulations supported by crystallographic data to assess the rigidity of bicyclopentane and cubane ring systems as two of the most common benzene bioisosteres and compares this to benzene. Whilst a benzene ring is shown to be more flexible than these two bioisosteres in terms of its dihedral ring flexibility, substituents around the ring tend to behave in a much more similar way in both benzene and the bioisosteric systems.

Sociodemographic inequities in the burden of carcinogenic industrial air emissions in the United States.

BACKGROUND: Industrial facilities are not located uniformly across communities in the United States, but how the burden of exposure to carcinogenic air emissions may vary across population characteristics is unclear. We evaluated differences in carcinogenic industrial pollution among major sociodemographic groups in the United States and Puerto Rico. METHODS: We evaluated cross-sectional associations of population characteristics including race and ethnicity, educational attainment, and poverty at the census tract level with point-source industrial emissions of 21 known human carcinogens using regulatory data from the US Environmental Protection Agency. Odds ratios and 95% confidence intervals comparing the highest emissions (tertile or quintile) to the referent group (zero emissions [ie, nonexposed]) for all sociodemographic characteristics were estimated using multinomial, population density-adjusted logistic regression models. RESULTS: In 2018, approximately 7.4 million people lived in census tracts with nearly 12 million pounds of carcinogenic air releases. The odds of tracts having the greatest burden of benzene, 1,3-butadiene, ethylene oxide, formaldehyde, trichloroethylene, and nickel emissions compared with nonexposed were 10%-20% higher for African American populations, whereas White populations were up to 18% less likely to live in tracts with the highest emissions. Among Hispanic and Latino populations, odds were 16%-21% higher for benzene, 1,3-butadiene, and ethylene oxide. Populations experiencing poverty or with less than high school education were associated with up to 51% higher burden, irrespective of race and ethnicity. CONCLUSIONS: Carcinogenic industrial emissions disproportionately impact African American and Hispanic and Latino populations and people with limited education or experiencing poverty thus representing a source of pollution that may contribute to observed cancer disparities.

Biological Evaluation of Isosteric Applicability of 1,3-Substituted Cuneanes as m-Substituted Benzenes Enabled by Selective Isomerization of 1,4-Substituted Cubanes.

We herein evaluate a biological applicability of 1,3-substituted cuneanes as an isostere of m-substituted benzenes based on its structural similarity. An investigation of a method to obtain 1,3-substituted cuneanes by selective isomerization of 1,4-substituted cubanes enables this attempt by giving a key synthetic step to obtain a cuneane analogs of pharmaceuticals having m-substituted benzene moiety. Biological evaluation of the synthesized analogs and in silico study of the obtained result revealed a potential usage of cuneane skeleton in medicinal chemistry.

Synthesis and Evaluation of 177Lu-DOTA-PD-L1-i and 225Ac-HEHA-PD-L1-i as Potential Radiopharmaceuticals for Tumor Microenvironment-Targeted Radiotherapy.

Current cancer therapies focus on reducing immunosuppression and remodeling the tumor microenvironment to inhibit metastasis, cancer progression, and therapeutic resistance. Programmed death receptor 1 (PD-1) is expressed on immune T cells and is one of the so-called checkpoint proteins that can suppress or stop the immune response. To evade the immune system, cancer cells overexpress a PD-1 inhibitor protein (PD-L1), which binds to the surface of T cells to activate signaling pathways that induce immune suppression. This research aimed to synthesize PD-L1 inhibitory peptides (PD-L1-i) labeled with lutetium-177 (177Lu-DOTA-PD-L1-i) and actinium-225 (225Ac-HEHA-PD-L1-i) and to preclinically evaluate their potential as radiopharmaceuticals for targeted radiotherapy at the tumor microenvironment level. Using PD-L1-i peptide as starting material, conjugation with HEHA-benzene-SCN and DOTA-benzene-SCN was performed to yield DOTA-PD-L1-i and HEHA-PD-L1-I, which were characterized by FT-IR, UV-vis spectroscopy, and HPLC. After labeling the conjugates with 225Ac and 177Lu, cellular uptake in HCC827 cancer cells (PD-L1 positive), conjugate specificity evaluation by immunofluorescence, radiotracer effect on cell viability, biodistribution, biokinetics, and assessment of radiation absorbed dose in mice with in duced lung micrometastases were performed. 225Ac-HEHA-PD-L1-i and 177Lu-DOTA-PD-L1-i, obtained with radiochemical purities of 95 ± 3% and 98.5 ± 0.5%, respectively, showed in vitro and in vivo specific recognition for the PD-L1 protein in lung cancer cells and high uptake in HCC287 lung micrometastases (>30% ID). The biokinetic profiles of 177Lu-DOTA-PD-L1-i and 225Ac-DOTA-PD-L1-i showed rapid blood clearance with renal and hepatobiliary elimination and no accumulation in normal tissues. 225Ac-DOTA-PD-L1-i produced a radiation dose of 5.15 mGy/MBq to lung micrometastases. In the case of 177Lu-DOTA-PD-L1-i, the radiation dose delivered to the lung micrometastases was ten times (43 mGy/MBq) that delivered to the kidneys (4.20 mGy/MBq) and fifty times that delivered to the liver (0.85 mGy/MBq). Therefore, the radiotherapeutic PD-L1-i ligands of 225Ac and 177Lu developed in this research could be combined with immunotherapy to enhance the therapeutic effect in various types of cancer.

Leukemia Mortality among Benzene-Exposed Workers in Brazil (2006-2011).

BACKGROUND: In this study, the annual leukemia mortality rate is estimated by occupational groups potentially exposed to benzene in Brazil and compared to non-exposed workers by sex. METHODS: Data were extracted from the Mortality Information System and the National Institute of Geography and Statistics from 2006 to 2011. Occupational groups exposed to benzene were defined by using the Finnish Job-Exposure Matrix, FINJEM. RESULTS: We found 21,049 leukemia deaths in 1917 in occupational groups potentially exposed to benzene, corresponding to an annual average mortality rate of 4.5/100,000, higher than the estimate for non-exposed workers: 2.6/100,000, corresponding to a Mortality rate ratio MRR = 1.7. Each benzene-exposed occupational group had increased leukemia mortality, and printers and occupations in graphics presented the highest MRR (2.7), followed by laboratory assistants (MRR = 2.6), laundry workers, chemists, and upholsterers, each of these occupational groups presenting MRR = 2.3. CONCLUSIONS: Benzene shows the need for better enforcement of protective norms against this known carcinogen. Our results support the need for better enforcement of protective norms to reduce benzene exposure.

Network Analysis of Biomarkers Associated with Occupational Exposure to Benzene and Malathion.

Complex diseases are associated with the effects of multiple genes, proteins, and biological pathways. In this context, the tools of Network Medicine are compatible as a platform to systematically explore not only the molecular complexity of a specific disease but may also lead to the identification of disease modules and pathways. Such an approach enables us to gain a better understanding of how environmental chemical exposures affect the function of human cells, providing better perceptions about the mechanisms involved and helping to monitor/prevent exposure and disease to chemicals such as benzene and malathion. We selected differentially expressed genes for exposure to benzene and malathion. The construction of interaction networks was carried out using GeneMANIA and STRING. Topological properties were calculated using MCODE, BiNGO, and CentiScaPe, and a Benzene network composed of 114 genes and 2415 interactions was obtained. After topological analysis, five networks were identified. In these subnets, the most interconnected nodes were identified as: IL-8, KLF6, KLF4, JUN, SERTAD1, and MT1H. In the Malathion network, composed of 67 proteins and 134 interactions, HRAS and STAT3 were the most interconnected nodes. Path analysis, combined with various types of high-throughput data, reflects biological processes more clearly and comprehensively than analyses involving the evaluation of individual genes. We emphasize the central roles played by several important hub genes obtained by exposure to benzene and malathion.

Volatile organic compounds measured by proton transfer reaction mass spectrometry over the complex terrain of Quintero Bay, Central Chile.

This research provides new evidence regarding the different kinds of air quality episodes, and their underlying mechanisms, that frequently impact the urban area of Quintero Bay in Central Chile, which is located along complex coastal terrain and is surrounded by industries. The monitoring campaign was carried out in January 2022 and encompassed two distinctive meteorological regimes. The first part of the month was dominated by a coastal low centered to the south of Quintero, which resulted in prevailing northerly flow (or weak southerlies) and a deep cloud-topped marine boundary layer. After a 2-3-day transition, the latter collapsed, and a clear-sky regime ensued, which was characterized by a shallow boundary layer and strong southerly winds during the daytime that lasted until the end of the campaign. By using proton transfer reaction time of flight mass spectrometry (PTR-TOF-MS) at a high temporal resolution (1 s), we measured high levels of volatile organic compounds (VOCs) during air quality episodes in real time. The episodes detected were associated with different prevailing meteorological regimes, suggesting that different point sources were involved. In the first episode, propene/cyclopropane, butenes, benzene, toluene and ethylbenzene/xylenes were associated with north and northwesterly weak winds. Complaints associated with hydrocarbon odor were reported. The pollution originated from industrial and petrochemical units located to the north of Quintero, which transport and store natural gas, liquified petroleum gas and oil. The second episode was linked to an oil refinery located south of our measurement site. In this case, high levels of phenol, furan and cresols occurred under strong southwesterly winds. During this event, headaches and dizziness were reported. By contrast, the levels of other aromatic compounds (benzene, toluene, ethylbenzene/xylenes) were lower than in the first air pollution episode.

Hematological Changes in Gas Station Workers.

(1) Background: Benzene, toluene, and xylene isomers (BTX) are present in gasoline. Exposure to benzene may lead to the appearance of a series of signs, symptoms, and complications, which are characterized by benzene poisoning, which is an occupational disease. This study evaluated the presence of signs and symptoms related to occupational exposure and whether occupational exposure to BTX is associated with the development of hematological changes. (2) Material and Methods: This cross-sectional epidemiological study included 542 participants, in which 324 were gas station workers (GSWs) and 218 were office workers (OWs) with no occupational exposure to benzene. To characterize the type of exposure (exposed and not exposed), trans,trans-Muconic acid (tt-MA), Hippuric acid (HA), and Methylhippuric acid (MHA) were used as exposure biomarkers. The tt-MA analysis revealed that the GSWs had 0.29 mg/g of urinary creatinine and the OWs had 0.13 mg/g of urinary creatinine. For HA, the GSWs presented 0.49 g/g of creatinine while the OWs presented 0.07. MHA analysis revealed that the GSWs had 1.57 g/g creatinine and the OWs had 0.01 g/g creatinine. Occupation habits and clinical symptoms were collected by questionnaire and blood samples were analyzed for hematological parameters. The persistence of hematological changes was evaluated with three serial blood collections every 15 days followed by laboratory hematological analysis. A descriptive analysis by the Chi-square test method was performed to evaluate the association between occupational exposure to fuels and the occurrence of changes in hematological parameters. (3) Results: In the GSWs, the most described signs and symptoms were somnolence (45.1%), headache (38.3%), dizziness (27.5%), tingling (25.4%), and involuntary movement (25%). Twenty GSWs that presented hematological alterations performed serial collections fifteen days apart. In addition, these workers presented total leukocyte counts above the upper limit and lymphocyte counts close to the lower limit. Leukocytosis and lymphopenia are hematological alterations present in chronic benzene poisoning. (4) Conclusions: The results found an initial change in different hematological parameters routinely used in clinics to evaluate health conditions. These findings reveal the importance of valuing clinical changes, even in the absence of disease, during the health monitoring of gas station workers and other groups that share the same space.

Study of a light hydrocarbon fraction spill migration that occurred in an area of the Mexican southeast using computational fluid dynamics.

The present work aimed to study, predict and understand benzene migration that occurred during an industrial spill using numerical simulation by computational fluid dynamics. Advection, diffusion and adsorption were the main mechanisms considered that governed the spill incident. The incident occurred due to a fracture under a fuel oil storage tank. The tank was located on a hill 18 m high, and the initial value of benzene concentration (soil saturation) was 60 ppm. When the spill was discovered, samples in the affected zone were taken using an experimental design. Many samples showed a greater concentration of benzene than allowed by Mexican Official Standards (MOSs) (15 ppm). The concentrations found 100 m away from the spill were around 60 to 15 ppm. Due to the spill being under the tank, it was difficult to discover. The numerical simulation provided an estimate that the spill started around 2 years ago. The type of soil in the afflicted zone is rocky, and, consequently, it is difficult to estimate how long it will take to reach the concentration allowed by the MOSs, but the numerical simulation predicts that this concentration will be reached in 14 years. Experimental values of the spill contaminant concentration were statistically similar to the CFD estimated data (p < 0.05).

Influence of Environmental Exposure to Steel Waste on Endocrine Dysregulation and PER3 Gene Polymorphisms.

OBJECTIVE: To evaluate the association between environmental exposure to the following chemical substances: cadmium (Cd), lead (Pb), nickel (Ni), manganese (Mn), benzene (BZN), and toluene (TLN), and Period Circadian Regulator 3 (PER3) gene variable number of tandem repeats (VNTR) polymorphisms, according to chronotype in a population living in a steel residue-contaminated area. METHODS: This assessment comprises a study conducted from 2017 to 2019 with 159 participants who completed health, work, and Pittsburgh sleep scale questionnaires. Cd, Pb, Ni, Mn, BZN, and TLN concentrations in blood and urine were determined by Graphite Furnace Atomic Absorption Spectrometry (GFAAS) and Headspace Gas Chromatography (GC), and genotyping was carried out using Polymerase Chain Reaction (PCR). RESULTS: A total of 47% of the participants were afternoon chronotype, 42% were indifferent, and 11% were morning chronotype. Insomnia and excessive sleepiness were associated with the indifferent chronotype, while higher urinary manganese levels were associated with the morning chronotype (Kruskal-Wallis chi-square = 9.16; p < 0.01). In turn, the evening chronotype was associated with poorer sleep quality, higher lead levels in blood, and BZN and TLN levels in urine (χ2 = 11.20; p < 0.01) in non-occupationally exposed individuals (χ2 = 6.98; p < 0.01) as well as the highest BZN (χ2 = 9.66; p < 0.01) and TLN (χ2 = 5.71; p < 0.01) levels detected in residents from the influence zone 2 (far from the slag). CONCLUSION: Mn, Pb, benzene, and toluene contaminants may have influenced the different chronotypes found in the steel residue-exposed population.

BTEX profile and health risk at the largest bulk port in Latin America, Paranaguá Port.

Port-related activities have a detrimental impact on the air quality both at the point of source and for considerable distances beyond. These activities include, but are not limited to, heavy cargo traffic, onboard, and at-berth emissions. Due to differences in construction, operation, location, and policies at ports, the site-specific air pollution cocktail could result in different human health risks. Thus, monitoring and evaluating such emissions are essential to predict the risk to the community. Environmental agencies often monitor key pollutants (PM2.5, PM10, NO2, SO2), but the volatile organic carbons (VOCs) most often are not, due to its analytical challenging. This study intends to fill that gap and evaluate the VOC emissions caused by activities related to the port of Paranaguá - one of the largest bulk ports in Latin America - by characterizing BTEX concentrations at the port and its surroundings. At seven different sites, passive samplers were used to measure the dispersion of BTEX concentrations throughout the port and around the city at weekly intervals from November 2018 to January 2019. The average and uncertainty of BTEX concentrations (µg m-3) were 0.60 ± 0.43, 5.58 ± 3.80, 3.30 ± 2.41, 4.66 ± 3.67, and 2.82 ± 1.95 for benzene, toluene, ethylbenzene, m- and p-xylene, and o-xylene, respectively. Relationships between toluene and benzene and health risk analysis were used to establish the potential effects of BTEX emissions on the population of the city of Paranaguá. Ratio analysis (T/B, B/T, m,p X/Et, and m,p X/B) indicate that the BTEX levels are mainly from fresh emission sources and that photochemical ageing was at minimum. The cancer risk varied across the sampling trajectory, whereas ethylbenzene represented a moderate cancer risk development for the exposed population in some of the locations. This study provided the necessary baseline data to support policymakers on how to change the circumstances of those currently at risk, putting in place a sustainable operation.

Evaluation of Bacillus subtilis as a Tool for Biodegrading Diesel Oil and Gasoline in Experimentally Contaminated Water and Soil.

Benzene, toluene, ethylbenzene and xylene (BTEX) are toxic petroleum hydrocarbons pollutants that can affect the central nervous system and even cause cancer. For that reason, studies regarding BTEX degradation are extremely important. Our study aimed evaluate the microorganism Bacillus subtilis as a tool for degrading petroleum hydrocarbons pollutants. Assays were run utilizing water or soil distinctly contaminated with gasoline and diesel oil, with and without B. subtilis. The ability of B. subtilis to degrade hydrophobic compounds was analyzed by Fourier-Transform Infrared Spectroscopy (FTIR) and gas chromatography. The FTIR results indicated, for water assays, that B. subtilis utilized the gasoline and diesel oil to produce the biosurfactant, and, as a consequence, performed a biodegradation process. In the same way, for soil assay, B. subtilis biodegraded the diesel oil. The gas chromatography results indicated, for gasoline in soil assay, the B. subtilis removed BTEX. So, B. subtilis was capable of degrading BTEX, producing biosurfactant and it can also be used for other industrial applications. Bioremediation can be an efficient, economical, and versatile alternative for BTEX contamination.

Health Risk Assessment in Children Occupationally and Para-Occupationally Exposed to Benzene Using a Reverse-Translation PBPK Model.

Benzene is a known human carcinogen and one of the ten chemicals of major public health concern identified by the World Health Organization. Our objective was to evaluate benzene's carcinogenic and non-carcinogenic health risks (current and projected) in highly exposed children in Yucatan, Mexico. Benzene exposure was estimated through a reverse-translation, four-compartment, physiologically based pharmacokinetic model (PBPK) based on previously performed urine trans, trans-muconic acid (benzene metabolite) determinations. Using a risk assessment methodology, the carcinogenic and non-carcinogenic risks of benzene were estimated for 6-12-year-old children from a family of shoemakers. The children's hazard quotients for decreased lymphocyte count were 27 and 53 for 4 and 8 h/day exposure, respectively, and 37 for the projected 8 h/day exposure in adults. The risks of developing leukemia were 2-6 cases in 1000 children exposed 4 h/day; 4-10 cases in 1000 children exposed 8 h/day, and 2-9 cases in 1000 adults with an 8 h/day lifetime exposure. Children in Yucatan working in shoe-manufacturing workshops, or living next to them, are exposed to benzene concentrations above the reference concentration and have unacceptably high risks of presenting with non-carcinogenic and carcinogenic hematologic symptoms, now and in the future. Interventions to prevent further exposure and mitigate health risks are necessary.

Caracterização da qualidade do ar atmosférico na Cidade de São Paulo para compostos do grupo BTEX (benzeno, tolueno, etilbenzeno e xilenos), utilizando amostradores passivos / Characterization of atmospheric air quality in the City of São Paulo for compounds of the BTEX group (benzene, toluene, ethylbenzene and xylenes), using passive samplers

A presença de compostos do grupo BTEX, no ar atmosférico de grandes centros urbanos como a cidade de São Paulo é proveniente principalmente de emissões veiculares e demais fontes como as industriais. A exposição a estes compostos, principalmente quando inalados, podem causar sérios efeitos adversos a saúde humana, especialmente o composto benzeno que possui propriedades cancerígenas. Desta forma, a presente pesquisa teve objetivo realizar uma caracterização da qualidade do ar atmosférico na cidade de São Paulo utilizando amostradores passivos para quantificação de compostos do grupo BTEX. Foram selecionadas 5 áreas na cidade conforme dados de tráfego destas regiões e de acordo com o perfil de uso e ocupação do solo. Adicionalmente, foi selecionada uma área como background, com interferência mínima de emissões veiculares ou industriais. Ao todo foram realizadas 3 campanhas de amostragem no entre os anos de 2020 e 2021. O período de coleta de cada campanha foi de 21 dias e na sequência as amostras foram enviadas para análise química em laboratório através do método USEPA-TO17, de 1999 com a utilização de dessorvedor térmico acoplado à um cromatógrafo de gás e um espectrômetro de massas. Foram quantificadas concentrações de BTEX em todas as áreas selecionadas, com destaque para as concentrações de benzeno cuja variação foi de 1,2µg/m3 a 13,5µg/m3, e média de 4,6µg/m3, considerando as 3 campanhas e todas as áreas. Dentro as áreas avaliadas, os pontos localizados no bairro de Santo Amaro apresentaram as maiores concentrações de BTEX, seguido dos pontos no Jaguaré, Mooca, Pinheiros e Paraíso. A campanha realizada no inverno de 2021 apresentou as maiores concentrações tendo influência das condições meteorológicas características desta estação como também influência do aumento do número de veículos circulando na cidade decorrente da diminuição do distanciamento social necessário por conta da pandemia da COVID-19. Os tratamentos estatísticos utilizados nesta pesquisa, especialmente as ferramentas PCA e PMF, concluíram que a principal contribuição para a presença dos BTEX no ar atmosférico são as emissões veiculares, principalmente para os veículos movidos a gasolina.

The presence of compounds from the BTEX group in the atmospheric air of large urban centers such as the city of São Paulo comes mainly from vehicular emissions and other sources such as industrial ones. Exposure to these compounds, especially when inhaled, can cause serious adverse effects on human health, especially the compound benzene, which has carcinogenic properties. Thus, the present research aimed to carry out a characterization of the atmospheric air quality in the city of São Paulo using passive samplers to quantify compounds of the BTEX group. Five areas were selected in the city according to traffic data from these regions and according to the profile of land use and occupation. Additionally, an area was selected as a background, with minimal interference from vehicular or industrial emissions. In all, 3 sampling campaigns were carried out between the years 2020 and 2021. The collection period of each campaign was 21 days and then the samples were sent for chemical analysis in the laboratory using the USEPA-TO17 method, from 1999 with the use of a thermal desorber coupled to a gas chromatograph and a mass spectrometer. BTEX concentrations were quantified in all selected areas, especially benzene concentrations which ranged from 1.2µg/m3 to 13.5µg/m3, and an average of 4.6µg/m3, considering the 3 campaigns and all areas. Within the evaluated areas, the points located in the Santo Amaro neighborhood had the highest concentrations of BTEX, followed by the points in Jaguaré, Mooca, Pinheiros and Paraíso. The campaign carried out in the winter of 2021 showed the highest concentrations influenced by the meteorological conditions characteristic of this season as well as the influence of the increase in the number of vehicles circulating in the city due to the decrease in the social distance necessary due to the COVID-19 pandemic. The statistical treatments used in this research, especially the PCA and PMF tools, concluded that the main contribution to the presence of BTEX in the atmospheric air are vehicular emissions, especially for gasoline-powered vehicles.

Engineered rHDL Nanoparticles as a Suitable Platform for Theranostic Applications.

Reconstituted high-density lipoproteins (rHDLs) can transport and specifically release drugs and imaging agents, mediated by the Scavenger Receptor Type B1 (SR-B1) present in a wide variety of tumor cells, providing convenient platforms for developing theranostic systems. Usually, phospholipids or Apo-A1 lipoproteins on the particle surfaces are the motifs used to conjugate molecules for the multifunctional purposes of the rHDL nanoparticles. Cholesterol has been less addressed as a region to bind molecules or functional groups to the rHDL surface. To maximize the efficacy and improve the radiolabeling of rHDL theranostic systems, we synthesized compounds with bifunctional agents covalently linked to cholesterol. This strategy means that the radionuclide was bound to the surface, while the therapeutic agent was encapsulated in the lipophilic core. In this research, HYNIC-S-(CH2)3-S-Cholesterol and DOTA-benzene-p-SC-NH-(CH2)2-NH-Cholesterol derivatives were synthesized to prepare nanoparticles (NPs) of HYNIC-rHDL and DOTA-rHDL, which can subsequently be linked to radionuclides for SPECT/PET imaging or targeted radiotherapy. HYNIC is used to complexing 99mTc and DOTA for labeling molecules with 111, 113mIn, 67, 68Ga, 177Lu, 161Tb, 225Ac, and 64Cu, among others. In vitro studies showed that the NPs of HYNIC-rHDL and DOTA-rHDL maintain specific recognition by SR-B1 and the ability to internalize and release, in the cytosol of cancer cells, the molecules carried in their core. The biodistribution in mice showed a similar behavior between rHDL (without surface modification) and HYNIC-rHDL, while DOTA-rHDL exhibited a different biodistribution pattern due to the significant reduction in the lipophilicity of the modified cholesterol molecule. Both systems demonstrated characteristics for the development of suitable theranostic platforms for personalized cancer treatment.

Theoretical study of keto-enol tautomerism in 7-epi-clusianone by quantum chemical calculations of NMR chemical shifts.

Plants from the Garcinia genus have been used worldwide due to their therapeutic properties. Among the various metabolites isolated from this genus, 7-epi-clusianone, a tetraprenylated benzophenone, stands out for its wide range of identified biological activities. This benzophenone can exist in five tautomeric forms, although the benzene-d6 and chloroform-d3 solution nuclear magnetic resonance (NMR) spectra revealed only two tautomeric forms (B and C) in equilibrium, with concentration ratio depending on the solvent in which the spectrum was obtained. Calculated energy values suggested that tautomeric forms B and E would be prevalent in benzene-d6 solution, in contrast to the experimental data. Considering this conflicting result, we employed the statistical DP4 + method based on 13C and 1H NMR chemical shift calculations, in the gas phase and in benzene-d6 solution, to confirm that the B and C tautomeric forms of 7-epi-clusianone are the most prevalent in the experimental conditions.

EFFECT OF DIFFERENT SOLVENTS ON THE OPTICALLY STIMULATED LUMINESCENCE SIGNAL FROM MGB4O7:CE,LI-LOADED POLYMER FILMS.

The detailed dose analysis at the extremities remains a challenge, without affecting operators' mobility and their tactile sense. Using films loaded with optically stimulated luminescence (OSL) crystals have been studied in order to overcome some of these challenges in 2D dosimetry. In this work, we investigated flexible polymeric films loaded with MgB4O7:Ce,Li to acquire a better understanding of the dependence of the dosimetric signal characteristics on the production process and the influence of using different powder grain sizes. In film production, five different solvents were used: acetone-benzene, dichloromethane, chloroform, tetrahydrofuran and formic acid. Our results indicate that acetone-benzene is the solvent mixture that less influences the signal emitted by treated crystals, in comparison with the signal emitted by the pristine crystal powder. Conversely, by using formic acid, the crystalline structure of the sample was most severely modified, leading to a drastic reduction of the emitted OSL signal. We found that the extent of the grain surface in contact with the solvent in the process is important and should be taken into consideration when choosing the proper grain size to be used. Highlights  Polymeric films loaded with MgB4O7:Ce,Li crystals were produced using different solvents.Different effect on the OSL signal was found depending on the used solvent.Among the evaluated solvents, acetone-benzene was the one that less affected the OSL signal.

Environmental and occupational exposure among cancer patients in Mato Grosso, Brazil.

OBJECTIVE: To estimate the prevalence of occupational and environmental exposure according to sociodemographic factors in cancer patients treated at reference hospitals in the state of Mato Grosso, Brazil. METHODS: This is a cross-sectional study on cancer patients aged 18 years or older. The prevalence of exposure to pesticides, asbestos, lead, heavy metals, formaldehyde, benzene, exposure to industrial dust, and handling of other chemical substances were calculated according to sex, age group, and level of education. RESULTS: A total of 1,012 patients were interviewed (55.0% women, 45.6% aged 60 years or older, and 56.8% had less than five years of formal education). Pesticides (22.8%), industrial dust (10.7%), and benzene (10.1%) were the most frequent exposures. Occupational and environmental exposure was higher in men for all evaluated exposures, except for formaldehyde, which was higher in women. Exposure to pesticides, industrial dust, benzene, asbestos, and heavy metals increased with age and were more frequent among those with lower level of education. CONCLUSION: Approximately one in five cancer patients treated at reference hospitals in Mato Grosso reported having been exposed to pesticides, and one in ten were exposed to industrial dust and benzene, with greater exposure among men, older individuals, and those with lower level of education.

Modeling the heating and cooling of a chromophore after photoexcitation.

The heating of a chromophore due to internal conversion and its cooling down due to energy dissipation to the solvent are crucial phenomena to characterize molecular photoprocesses. In this work, we simulated the ab initio nonadiabatic dynamics of cytosine, a prototypical chromophore undergoing ultrafast internal conversion, in three solvents-argon matrix, benzene, and water-spanning an extensive range of interactions. We implemented an analytical energy-transfer model to analyze these data and extract heating and cooling times. The model accounts for nonadiabatic effects, and excited- and ground-state energy transfer, and can analyze data from any dataset containing kinetic energy as a function of time. Cytosine heats up in the subpicosecond scale and cools down within 25, 4, and 1.3 ps in argon, benzene, and water, respectively. The time constants reveal that a significant fraction of the benzene and water heating occurs while cytosine is still electronically excited.