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Background Sleep is a crucial physiological activity for the human body, and research has shown that air pollution can affect sleep quality. However, the association between polycyclic aromatic hydrocarbons (PAHs) exposure, neurotoxic compounds in air pollutants, and sleep quality remains uncertain. Objective To evaluate the association of PAHs exposure with sleep quality, and to provide evidence for improving sleep quality. Methods This study used a cross-sectional design. We selected 632 workers from a coking plant of a large state-owned enterprise as the exposure group, and 477 workers from the energy and power plant of the same enterprise as the control group. All workers worked in three shifts. A questionnaire survey was conducted to collect basic information including gender, years of service, age, educational level, smoking, alcohol consumption, consumption of fried foods, cooking frequency, types of cooking fuels. Worker's post-shift morning midstream urine was sampled to determine the concentrations of eight PAHs metabolites (OH-PAHs) using gas chromatography-tandem mass spectrometry (GC-MS). Worker's sleep quality was assessed using Pittsburgh Sleep Quality Index (PSQI). A higher PSQI score indicated a lower sleep quality. Associations of urinary OH-PAHs levels with sleep quality in the workers were analyzed using linear regression, Bayesian kernel-machine regression (BKMR), and quantile g-computation. Results The median (P25, P75) concentration of total OH-PAHs in the exposure group [88.84 (46.27, 151.96) μg·L−1] was higher than that in the control group [54.33 (24.86, 97.97) μg·L−1]. Additionally, the PSQI score (\begin{document}$ \overline{x}\pm {s} $\end{document}) in the exposure group (5.16±3.84) was higher than that in the control group (4.60±3.17). The multiple linear regression revealed that an increase in the sum of the concentrations of eight OH-PAHs after natural logarithmic transformation (lnΣ8OH-PAHs) was associated with an increase of 0.3646 (95%CI: 0.1337, 0.5955) in PSQI score, and an increase in lnΣlow-ring OH-PAHs was associated with an increase of 0.2954 (95%CI: 0.0941, 0.4967) in PSQI score. The BKMR analysis demonstrated that PSQI score was gradually increased as the increasing of lnΣ8OH-PAHs concentration. The quantile g-computation analysis indicated that a quantile increase in lnΣ8OH-PAHs concentration was associated with an increase of 0.4062% (95%CI: 0.1176%, 0.6949%) in PSQI score. Conclusion Compared to the controls, the coking workers show a higher concentration of urinary OH-PAHs and report worse sleep quality. The concentration of OH-PAHs is significantly negatively associated with sleep quality.
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En el presente trabajo se estudia la actividad horaria de los mamíferos que habitan el área circundante a la línea transportadora de gas de Camisea que atraviesa la Reserva Comunal Machiguenga. Desde febrero del 2020 hasta enero del 2021, se realizó un registro fotográfico mediante cámaras trampa dispuestas a lo largo de la tubería de gas. Los patrones de actividad se estimaron mediante la función de densidad de Kernel. Durante el periodo de estudio, se registraron 25 especies de mamíferos. Se encontró que Dasyprocta kalinowskii y Eira barbara presentan un patrón de actividad diurno; mientras que Cuniculus paca, Tapirus terrestris, Dasypus spp. y Mazama spp. presentan un patrón predominantemente nocturno. Se sugiere que los patrones de actividad observados estarían influenciados por varios factores como la exclusión competitiva entre D. kalinowskii y C. paca, disponibilidad estacional del alimento para T. terrestris, variación de temperatura y precipitación para Dasypus spp., restricciones filogenéticas en Mazama spp., y segregación temporal con otros carnívoros para E. barbara. Se destaca la importancia de la colaboración entre las empresas del rubro energético, las comunidades nativas y las organizaciones gubernamentales.
The present study investigates the hourly activity patterns of mammals inhabiting the area surrounding the Camisea gas pipeline that crosses the Machiguenga Communal Reserve. From February 2020 to January 2021, a photographic record was conducted using camera traps placed along the gas pipeline. Activity patterns were estimated using Kernel density functions. During the study period, 25 mammal species were recorded. It was found that Dasyprocta kalinowskii and Eira barbara exhibit a diurnal activity pattern, whereas Cuniculus paca, Tapirus terrestris, Dasypus spp., and Mazama spp. display predominantly nocturnal behavior. It is suggested that observed activity patterns could be influenced by various factors such as competitive exclusion between D. kalinowskii and C. paca, seasonal food availability for T. terrestris, temperature and precipitation variations for Dasypus spp., phylogenetic constraints in Mazama spp., and temporal segregation with other carnivores for E. barbara. The significance of collaboration between energy industry companies, native communities, and governmental organizations is emphasized.
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SUMMARY: Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is highly expressed in various types of cancers including breast cancer. However, the role of AhR with its endogenous ligand 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) on the progression of breast cancer remains poorly understood. We aimed to investigate cell proliferation and migration states in breast cancer after activating AhR with the endogenous ligand ITE. Breast cancer tissue was evaluated by cell lines, immunohistochemistry, reverse transcription-polymerase chain reaction, cell proliferation, flow cytometry, migration assays and western blot techniques. We found that AhR was widely expressed in breast cancer tissues and metastasis lymph node tissues, but not in normal tissues. The expression AhR was independent between the age, grades and TNM classifications for breast cancer tissues. ITE treatment significantly induced the activation of AhR in a time-dependent manner in both MCF-7 and T47D breast cancer cell lines. Meanwhile, ITE did not affect the cell migration but significantly suppressed the cell proliferation in estrogen receptor positive (ER+) MCF-7 andT47D cells, which probably attribute to the induction of cell cycle arrest in G1 phase and shortened S phase. Further mechanism study showed that ERK1/2 and AKT signaling were required for the activation of AhR in MCF-7 cells. These data suggest that AhR is a potential new target for treating patients with breast cancer. ITE may be more potentially used for therapeutic intervention for breast cancer with the kind of ER(+).
El receptor de hidrocarburo de arilo (AhR) es un factor de transcripción activado por ligando que se expresa en gran medida en varios tipos de cáncer, incluido el cáncer de mama. Sin embargo, el papel de AhR con su ligando endógeno 2- (1'H-indol-3'-carbonil)-tiazol-4-ácido carboxílico metil éster (ITE) en la progresión del cáncer de mama sigue siendo poco conocido. Nuestro objetivo fue investigar la proliferación celular y los estados de migración en el cáncer de mama después de activar AhR con el ligando endógeno ITE. El tejido de cáncer de mama se evaluó mediante líneas celulares, inmunohistoquímica, reacción en cadena de la polimerasa con transcriptasa inversa, proliferación celular, citometría de flujo, ensayos de migración y técnicas de transferencia Western. Descubrimos que AhR se expresó ampliamente en tejidos de cáncer de mama y en linfonodos con metástasis, pero no en tejidos normales. La expresión AhR fue independiente entre la edad, grados y clasificaciones TNM para tejidos de cáncer de mama. El tratamiento con ITE indujo significativamente la activación de AhR de manera dependiente del tiempo en las líneas celulares de cancer de mama MCF-7 y T47D. Mientras tanto, ITE no afectó la migración celular, pero suprimió significativamente la proliferación celular en células MCF-7 y T47D con receptor de estrógeno positivo (ER+), lo que probablemente se atribuye a la inducción de la detención del ciclo celular en la fase G1 y la fase S acortada. Un estudio adicional del mecanismo mostró que las señales de ERK1/2 y AKT eran necesarias para la activación de AhR en las células MCF-7. Estos datos sugieren que AhR es un nuevo objetivo potencial para el tratamiento de pacientes con cáncer de mama. ITE puede ser utilizado más potencialmente en la intervención terapéutica para el cáncer de mama con el tipo de ER (+).
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Humans , Female , Thiazoles/administration & dosage , Breast Neoplasms/pathology , Receptors, Aryl Hydrocarbon/drug effects , Indoles/administration & dosage , Thiazoles/pharmacology , Immunohistochemistry , Receptors, Estrogen , Blotting, Western , Cytochrome P-450 CYP1A1/genetics , Cell Line, Tumor/drug effects , Cell Proliferation/drug effects , Cell Migration Assays , Cytochrome P-450 CYP1B1/genetics , Flow Cytometry , Indoles/pharmacologyABSTRACT
Aim: The Total Hydrocarbon Content (THC) levels in the leaves of three edible plants (Allium cepa, Telfairia occidentalis and Zea mays) grown on soil polluted with 100 ml of crude oil were examined. Study Design: This experiment was conducted in two groups where the soil samples were polluted before planting (PB) and polluted 2 weeks after planting (PA). Place and Duration of Study: The research was carried out at the Federal University of Technology, Owerri (FUTO), Imo State, Nigeria, within a period of 4 weeks based on each group’s pollution time. Methodology: The tests for total hydrocarbon content (THC) were analyzed at different wavelengths for polluted soil and leaf samples using UV-Vis spectrophotometric method. Soil THC tests were determined on days 0, 14 and 28 respectively while THC tests on leaves of study plants were assessed on day 14 and 28. Results: The total hydrocarbon content values of the unpolluted soil (UPS) and the non-planted polluted soil (PS) subjected to this analysis on day zero were (UPS = 96.38 mg/kg; PS = 1082.80 mg/kg). However, results obtained on day 14 and 28 showed significant difference (P < 0.05) between the unpolluted soil sample (UPS) and all the planted polluted soil for Telfairia occidentalis (TOPB, TOPA), Allium cepa (ACPB, ACPA), Zea mays (ZMPB, ZMPA) as well as, the non-planted polluted soil (PS). For the leaf samples, TOPB had the highest THC value of 14.47mg/kg and 36.73 mg/kg for day 14 and 28 respectively while ZMPB had the lowest value of 5.38mg/kg at day 14 and ZMPA, the least THC value of 7.76mg/kg at day 28. Conclusion: Based on the varying THC levels observed in the leaves of crops used for this study; it was connoted that, bioaccumulation of hydrocarbons depends on the plants phytoremediation capability and the mode of pollution as observed in TOPB.
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Objective:To evaluate the role of aryl hydrocarbon receptor (AhR) in the down-regulation of Clara cell secretory protein (CCSP) expression during endotoxin-induced lung injury in rats.Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 200-250 g, were divided into 4 groups ( n=6 each) using a random number table method: normal control group (group C), acute lung injury (ALI) group, ALI+ AhR antagonist group, and ALI+ vehicle group. Lipopolysaccharide(LPS) 1 mg/kg was intratracheally instilled to develop the model of lung injury, while the equal volume of normal saline was given instead in group C. At 2 h before LPS injection, AhR antagonist 6, 2′, 4′-trimethoxyflavone solution 5 mg/kg (diluted to 1 ml in dimethyl sulfoxide solution) was intraperitoneally injected in ALI+ AhR antagonist group, while dimethyl sulfoxide solution 1 ml was given in ALI+ vehicle group. The rats were sacrificed under anesthesia at 48 h after LPS administration. The left lung was lavaged and the broncho-alveolar lavage fluid (BALF) was collected for determination of the concentrations of CCSP by enzyme-linked immunosorbent assay, and the expression of CCSP in the bronchial epithelium in right lung tissues was determined by immunohistochemistry. Results:Compared with group C, the expression of CCSP in the bronchial epithelium was significantly down-regulated, and the concentrations of CCSP in BALF were decreased in the other three groups ( P<0.05 or 0.01). Compared with ALI group and ALI+ vehicle group, the histopathological injury was significantly reduced, the expression of CCSP in the bronchial epithelium was up-regulated, and the concentrations of CCSP in BALF were increased in ALI+ AhR antagonist group ( P<0.01). Conclusions:AhR partially mediates the down-regulation of CCSP expression during endotoxin-induced lung injury in rats.
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Objective:To investigate the risk factors and their warning value for the occurrence of sepsis in patients with severe multiple trauma.Methods:A retrospective cohort study was conducted to analyze the clinical data of 92 patients with severe multiple trauma admitted to Yuyao People′s Hospital from July 2019 to October 2021. There were 71 males and 21 females, with the age range of 36-55 years [(45.5±13.6)years]. The injury severity score (ISS) was 20-29 points [(25.3±6.4)points]. The patients were divided into sepsis group ( n=32) and non-sepsis group ( n=60) according to whether sepsis occurred during hospitalization. Data were recorded for the two groups, including gender, age, basic diseases, cause of injury, number of injury sites, ISS, post-injury complications, and levels of aryl hydrocarbon receptor (AHR), C-reactive protein (CRP) and procalcitonin (PCT) at 1, 3 and 5 days after injury. The above data were analyzed to identify their correlation with the occurrence of sepsis in patients with severe multiple trauma by univariate analysis. The independent risk factors for sepsis in patients with severe multiple trauma were determined by multivariate Logistic regression analysis. The warning value of the single or combined risk factors for the occurrence of sepsis in patients with severe multiple trauma was evaluated by the receiver operating characteristic (ROC) curve and area under the curve (AUC). Results:By univariate analysis, it was demonstrated that the occurrence of sepsis was correlated with ISS, level of AHR at day 1 after injury, level of CRP at day 3 after injury and level of PCT at day 3 after injury ( P<0.05 or 0.01), but not with age, sex, basic diseases, level of AHR at 3, 5 days after injury, level of PCT at 1, 5 days after injury and level of CRP at 1, 5 days after injury (all P>0.05). By multivariate Logistic regression analysis, higher ISS ( OR=1.12, 95% CI 1.01, 1.24, P<0.05), level of AHR at day 1 after injury ( OR=1.30, 95% CI 1.10, 1.52, P<0.01) and level of PCT at day 3 after injury ( OR=1.81, 95% CI 1.08, 3.03, P<0.05) were found to be strongly correlated with the occurrence of sepsis. ROC curve analysis showed that higher ISS (AUC=0.69, 95% CI 0.57, 0.76) and level of AHR at day 1 after injury (AUC=0.79, 95% CI 0.68, 0.90) had warning value for the occurrence of sepsis, and the warning efficiency of combined panel was much better (AUC=0.86, 95% CI 0.77, 0.95). Conclusions:Higher ISS, level of AHR at day 1 after injury and level of PCT at day 3 after injury are independent risk factors for the occurrence of sepsis in patients with severe multiple trauma. ISS, AHR and combination of both exhibit good warning value for the occurrence of sepsis in patients with severe multiple trauma.
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Aim To investigate the effect of the aryl hydrocarbon receptor (AhR) on the expression of inflammatory factors in macrophages RAW264. 7 induced by pyocyanin (PCN) and the regulatory mechanism of its signaling pathway. Methods RAW264. 7 cells were treated with different concentrations of PCN for 24 h, respectively, and the effect of PCN on cell activity was detected by CCK8 assay to determine the optimal PCN concentration for manufacturing infection models. The cells were divided into the control group (given 0. 1% dimethyl sulfoxide DMSO), PCN group, PCN + AhR inhibitor (CH223191) group, and PCN + AhR agonist (FICZ) group, and the expression of AhR was detected by immunofluorescence. The expression levels of inflammatory factors (IL-6, IL-1β, and TNF-α) were detected by ELISA. The protein expression of AhR, pp38 MAPK and p-p65NF-κB, was detected by Western blotting. Results PCN induced a significant quantitative effect on AhR expression in RAW264. 7 cells. CH223191 increased PCN-induced inflammatory factor secretion and enhanced the phosphorylation of p38MAPK and p65NF-κB compared with the control group. FICZ decreased PCN-induced inflammatory factor production and reduced the phosphorylation of p38MAPK and p65NF-κB phosphorylation capacity. Conclusions AhR can regulate PCN-induced inflammatory factor expression in RAW264. 7 cells, and the p38MAPK/p65NF-κB signaling pathway may be an essential pathway for the involvement of AhR in immune regulation.
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Objective To explore the biological exposure limit of blood system damage caused by long-term exposure to polycyclic aromatic hydrocarbons (PAHs) in non-occupational population by using the benchmark dose method, and to provide relevant reference for further improving the assessment of PAHs-induced health damage effects. Methods Adult residents living in downwind direction of a coke-oven plant in Shanxi Province were selected as the research subjects, and the information collected from baseline was used as the control. The metabolites of PAHs in urine were used as exposure biomarker, and the abnormal rate of red blood cell index was used as response biomarker. The relationship between urinary OH-PAHs and the erythrocyte damage rate was analyzed, and the benchmark dose (BMD) and the lower confidence limitation for the benchmark dose (BMDL) were calculated using Bayesian dose-optimizing software. Results The urinary PAH metabolites were mainly naphthalene and fluorene. The detection concentrations of 2-OHFlu and 1-OHPhe in the final year were higher than those in the baseline (P<0.05). With the increase of exposure years, the abnormal rate of red blood cells in the final year was higher than that in the baseline (P<0.05). In addition, the abnormal rate of red blood cells increased with the increase of the concentrations of five metabolites of PAHs in urine, and the chi-square trend test was significant (P<0.05). The benchmark dose (BMD) of OH-PAHs was 0.67 μmol/mol Cr, 0.82 μmol/mol Cr, 1.40 μmol/mol Cr and 0.78 μmol/mol Cr, respectively. The BMD of 2-OHNap in people with barbecue diet habits was 0.23 μmol/mol Cr. The BMD of 2-OHNap in people without barbecue diet habits was 1.44 μmol/mol Cr. Conclusion There is a dose-response relationship between the concentration of PAHs metabolites in urine and the damage of red blood cells. Long-term exposure to PAHs can lead to hematological damage. It is suggested that targeted public health interventions should be formulated to reduce the exposure of the general population to PAHs.
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Background Due to the limited availability of established research models, very few studies addressed the health effects and underlying mechanisms following exposure to diesel exhaust during the initiation of pulmonary respiration. It is highly demanded to elucidate such health effects and underlying mechanisms, so as to exert protective measures during the early stages of life. Objective To evaluate the health effects of diesel exhaust very-early-in-life inhalation in hatchling chicken with a novel chicken embryo air cell inhalation exposure model, and to explore the potential roles of aryl hydrocarbon receptor signaling pathways in the observed effects with a specific aryl hydrocarbon receptor inhibitor. Methods Fertilized chicken eggs were assigned into five groups randomly (15 eggs per group): control group, air control group, aryl hydrocarbon receptor inhibitor (PDM2) group, diesel exhaust group, and diesel exhaust + aryl hydrocarbon receptor inhibitor (PDM2) group. Fertilized eggs were incubated with standard procedure. At embryonic day 17 (ED17), aryl hydrocarbon receptor inhibitor was administered to the corresponding animals. During embryonic day 18-19 (ED18-19), chicken embryos were exposed to diesel exhaust via air cell inhalation, then placed back to incubator until hatch. The air control group received clean air infusion during ED18-19, while the control group did not receive any treatment. Within 24 h post-hatch, 26 hatchling chickens were anesthetized with sodium pentobarbital, subjected to electrocardiography, and sacrificed to harvest tissue samples of heart and lung. Cardiopulmonary toxicities were evaluated by histopathology, and potential changes in the protein expression levels of aryl hydrocarbon receptor pathway molecule cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) and fibrosis-related pathway molecule phosphorylated SMAD family member 2 (pSMAD2) were assessed by Western blotting. The remaining 29 hatchling chickens were reared until two weeks old, and then subjected to identical treatments. Results The inhalation exposure to diesel exhaust at initiation of pulmonary respiration resulted in thickened right ventricular wall (by 220.3% relative to the control group, same hereafter) and elevated heart rate (17.4%) in one-day-old hatchling chickens. Although no remarkable fibrotic lesions were observed at this point, the expression levels of CYP1A1 and phosphorylation levels of SMAD2 in the lung tissues significantly increased (by 81.3% and 71.6%, respectively). Such changes were effectively abolished by the aryl hydrocarbon receptor inhibitor PDM2 pretreatment. In the two-week-old animals, the thickened right ventricular wall (by 339.3%) and elevated heart rate (by 18.9%) persisted, and significant fibrotic lesions were observed in the lung tissue samples under Masson staining. Again, the aryl hydrocarbon receptor inhibitor PDM2 pretreatment effectively abolished such changes. In addition, no statistically significant changes in CYP1A1 expression levels were observed in the two-week-old chicken lung samples, and a remarkable down-regulation of SMAD2 phosphorylation was observed. The aryl hydrocarbon receptor inhibitor PDM2 pretreatment independently decreased the phosphorylation levels of SMAD2 in the two-week-old chicken lung samples. Conclusion Inhalation exposure to diesel exhaust at initiation of pulmonary respiration could result in persistent cardiopulmonary injury in hatchling chickens, and the underlying mechanism might be associated with the regulation of pSMAD2 by the aryl hydrocarbon receptor signaling pathway.
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The comparative study of poultry wastes- and HBB5 biosurfactant-mediated polyaromatic hydrocarbon biodegradation in sediment polluted with crude oil were investigated. The experiments were carried out for a period of 28 days by monitoring pH, nitrate, phosphate, polycyclic aromatic hydrocarbon and microbiological parameters using standard procedures. The pH values obtained ranged between 6.21 and 6.93 in days 1 and 28 for the most effective treatment recipes. Generally, there was depletion in the concentrations of nitrate and phosphate for all set ups, but the most effective recipe witnessed highest reduction. For the polycyclic aromatic hydrocarbons, the recipe with highest limiting nutrients depletion also recorded the most hydrocarbon loss, and yet highest increase in density of hydrocarbonoclastic bacteria and fungi. The sample containing polluted sediment + poultry wastes + HBB5 biosurfactant recorded PAH values of 1932.6472ppm on day 1 and 481.2272ppm on day 28. Total hydrocarbon-utilizing bacterial counts ranged from 1.48×104 cfu/g to 9.70×106 cfu/g, while hydrocarbon-utilizing fungal counts ranged between 2.30×103 cfu/g and 3.90×105 cfu/g. From the results obtained, poultry wastes combined with HBB5 biosurfactant recorded the highest efficiency in the biodegradation of polycyclic aromatic hydrocarbons in sediments, and HBB5 biosurfactant in isolation recorded higher degradation efficiency for polyaromatic hydrocarbons than the degradation effect mediated by poultry wastes alone. It is therefore recommended that a combination of surface-active agent, nutrient amendment source and viable microbial biomass be adopted and employed as potent recipe for the degradation of polyaromatic hydrocarbons in crude oil-contaminated sediments.
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Tapinarof is a novel topical formulation approved recently, in May 2022, by the United States Food and Drug Administration to treat plaque psoriasis. Existing topical therapies for psoriasis are limited by systemic and local adverse effects, medication cost and repeated administration, thus significantly hampering the compliance of patients to therapy. These limitations can be resolved by tapinarof owing to its better efficacy and favourable safety profile in psoriasis management. Tapinarof was developed with a unique mechanism targeting the aryl hydrocarbon receptor (AhR) involved in inflammation and modulation of skin barrier integrity in inflammatory dermatological disorders such as psoriasis and atopic dermatitis. The efficacy and safety outcomes of tapinarof in psoriasis were justified through the two pivotal clinical trials, namely, PSOARING 1 and PSOARING 2. The common adverse effects observed with tapinarof are folliculitis, contact dermatitis and headache. The literature search was conducted for efficacy and safety of tapinarof in the electronic databases of PubMed and Cochrane using a combination of keywords such as tapinarof, psoriasis and AhR. This review will delineate the molecular mechanisms underlying the action of tapinarof and also summarise the trial data supporting the claim that tapinarof is replacing the existing standard of care in psoriasis management.
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Resumen En la industria petrolera se almacenan grandes cantidades de hidrocarburos en tanques en las diferentes etapas de extracción y procesamiento del crudo hasta su refinamiento. Esto genera un residuo denominado fondo de tanque, es una emulsión estable de sedimentos agua e hidrocarburos. Este trabajo tuvo como objeto estudiar las bacterias que están presentes en el sedimento después de la primera etapa de tratamiento con gasoil, agua, temperatura y posterior centrifugación. El sedimento, considerado por la legislación como residuo peligroso se le realizo un estudio bacteriológico, que consistió en recuento, aislamiento e identifican de bacterias. Se obtuvieron 34 cepas de las cuales 86.1% pertenecieron al género Bacillus. Las mismas presentaron capacidad para desarrollar en alguno de los siguientes hidrocarburos o mezclas de hidrocarburos gasoil, kerosene, hexadecano y ciclohexano.
Abstract In the oil industry, large quantities of hydrocarbons are stored in tanks, in the different stages of extraction and processing of crude oil until it is refined. This generates a residue called a tank bottom, which is a stable emulsion of water and hydrocarbon sediments. The objective of this work was to study the bacteria that are present in the sediment after treating the bottom of the tank with diesel oil, water, and subsequent centrifugation. A bottom and tank were treated with diesel, water and centrifugation, the sediment was obtained, which was counted, isolated and bacteria were identified. 34 strains were obtained, of which 86.1% belonged to the genus Bacillus. The same capacity capabilities to develop diesel, kerosene, hexadecane, and cyclohexane hydrocarbons.
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Tumor cells have unique metabolic programming that is biologically distinct from that of corresponding normal cells. Resetting tumor metabolic programming is a promising strategy to ameliorate drug resistance and improve the tumor microenvironment. Here, we show that carboxyamidotriazole (CAI), an anticancer drug, can function as a metabolic modulator that decreases glucose and lipid metabolism and increases the dependency of colon cancer cells on glutamine metabolism. CAI suppressed glucose and lipid metabolism utilization, causing inhibition of mitochondrial respiratory chain complex I, thus producing reactive oxygen species (ROS). In parallel, activation of the aryl hydrocarbon receptor (AhR) increased glutamine uptake via the transporter SLC1A5, which could activate the ROS-scavenging enzyme glutathione peroxidase. As a result, combined use of inhibitors of GLS/GDH1, CAI could effectively restrict colorectal cancer (CRC) energy metabolism. These data illuminate a new antitumor mechanism of CAI, suggesting a new strategy for CRC metabolic reprogramming treatment.
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Objective:To explore the value of microRNA(miR)-124-3p and its target gene aryl hydrocarbon receptor (AHR) in the diagnosis and prognostic evaluation of gastric cancer, and the related molecular mechanisms in regulating proliferation and invasion of gastric cancer cell.Methods:The clinical and prognostic characteristics of patients with gastric adenocarcinoma expressing miR-124-3p were obtained from The Cancer Genome Atlas database and Genotype-Tissue Expression database. The correlation between miR-124-3p expression level and pathological stage, TNM stage, overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) in patients with gastric adenocarcinoma were studied by bioinformatics analysis. The interaction sites between miR-124-3p and AHR mRNA were predicted by Target Scan 7.1 online tool. The target binding sites of miR-124-3p in AHR mRNA were verified by subcutaneous tumorigenesis experiment in mice, immunohistochemistry, dual luciferase assay, quantitative real time-polymerase chain reaction (RT-qPCR) and Western blotting. Nine male Balb/c nude mice, aged 4 to 6 weeks with weight of (18.43±0.29) g were injected with miR-124-3p simulant (miR-124-3p group), negative control simulant (negative control group) and 0.9% sodium chloride solution (sodium chloride control group) through the tail vein. Gastric cancer cell lines (MKN-45, AGS) were transfected with RNA simulants (including miR-124-3p simulant, negative control simulant and 0.9% sodium chloride solution). The expression of AHR and Catenin β 1 gene ( CTNNB1) at mRNA level, the expression of AHR and β-catenin at protein level in 3 mice groups and the effects of miR-124-3p transfection on the proliferation and invasion of transfected gastric cancer cells were analyzed. Pearson correlation analysis and Holm-Sidak corrected multiple t test were used for statistical analysis. Results:Low expression of miR-124-3p was positively correlated with severe pathological stages and TNM stages in patients with gastric adenocarcinoma ( R2=0.83 and 0.86, P=0.031 and 0.023). High expression of miR-124-3p was positively correlated with OS, DSS and PFI ( R2=1.00, 0.99 and 0.99, P=0.029, 0.044 and 0.049). The results of subcutaneous tumorigenesis experiment in mice demonstrated that the number of apoptotic cells in the tumor of miR-124-3p group was more than that of negative control group and sodium chloride control group ((43.33±1.86)/high power field (HPF) vs. (20.00±1.73)/HPF and (18.67±1.76)/HPF), and the differences were statistically significant ( t=8.55 and 8.33, P=0.013 and 0.014). The results of immunohistochemistry showed that the optical density of AHR protein in mice tumor tissue of miR-124-3p group was lower than that of negative control group and sodium chloride control group (0.081±0.008 vs. 0.276±0.019 and 0.273±0.018), and the differences were statistically significant ( t=9.06 and 7.51, P=0.012 and 0.017). The results of dual luciferase assay indicated that the fluorescence intensity in wild-type AHR MKN-45 cells transfected with miR-124-3p simulant was lower than that of negative control group (0.293±0.020 vs. 1.000±0.032), and the difference was statistically significant ( t=18.56, P<0.001). The results of RT-qPCR demonstrated that the mRNA levels of AHR and CTNNB1 in MKN-45 cells transfected with miR-124-3p simulant were both lower than those in untreated MKN-45 cells (0.51±0.09 vs. 1.02±0.02, 0.46±0.03 vs. 1.03±0.01), and the differences were statistically significant ( t=4.51 and 16.60, P=0.046 and 0.004). The results of Western blotting experiments showed that the relative protein expression levels of AHR and β-catenin of MKN-45 cells transfected with miR-124-3p simulant were lower than those of transfected with 0.9% sodium chloride solution and negative control simulant (3 332.94±81.25 vs. 9 041.60±439.79 and 8 276.54±562.52, 2 725.79±167.57 vs. 9 701.94±410.02 and 8 081.66±275.84), and the differences were statistically significant ( t=15.49, 7.91, 17.35 and 19.42, P=0.004, 0.016, 0.003 and 0.003). Conclusions:MiR-124-3p is correlated with diagnosis and prognosis of gastric cancer. MiR-124-3p induces apoptosis of gastric cancer cells in vitro and vivo by negatively regulating AHR expression at mRNA and protein level, thereby down-regulating the expression of CTNNB1 mRNA and β-catenin pathway-related protein. Therefore, miR-124-3p may become a potential diagnostic and prognostic marker of gastric cancer.
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ObjectiveTo explore the role of aryl hydrocarbon receptor/suppressor of cytokine signaling 2/nuclear transcription factor-κB (AHR/SOCS2/NF-κB) signaling in the reduction of spinal cord injury (SCI) inflammation with every-other-day fasting (EODF). MethodsA total of 36 healthy male Sprague-Dawley rats were randomly divided into sham group (n = 12), model group (n = 12) and EODF group (n = 12). The latter two groups were established C5 spinal cord hemi-clamp model. The EODF group received EODF, namely fasting and feeding per 24 hours (water free), for two weeks after operation. They were assessed with Grooming Test before operation, and one, seven and 14 days after operationt, respectively. Pathological injury of spinal cord was observed with HE staining 14 days after operation, while the expression of AHR, SOCS2 and NF-κB proteins were detected with Western blotting, and the mRNA of AHR, SOCS2, inhibitor α of NF-κB (IκBα), NF-κB and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) were measured with reverse transcription real-time quantitative polymerase chain reaction. ResultsCompared with the sham group, the Grooming Test score decreased in the other two groups (P < 0.05), and cavity, edema and structural disorder appeared in the spinal cord. Compared with the model group, the pathology of EODF group improved, and the Grooming Test score increased (P < 0.05). The mRNA and protein expression of AHR and SOCS2 increased (P < 0.05), the mRNA and protein expression of NF-κB decreased (P < 0.05), the mRNA expression of IκBα increased (P < 0.05), and the mRNA expression of TNF-α and IL-6 decreased (P < 0.05). ConclusionEODF may promote the recovery of motor function of forelimb in rats with SCI, and relieve damage and inflammation, which may associate with the activation of AHR/SOCS2/NF-κB signaling pathway.
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@#Excellent mechanical properties and biocompatibility resulted in titanium and titanium alloys being widely used in the medical field. However, the biological activity of atitanium surface will gradually fade with increasing exposure time, which affects its final osseointegration. As an effective surface modification method, ultraviolet (UV) photofunctionalization does not change the surface morphology of implants and is a suitable surface treatment for many brands of implants. This article summarizes the research progress on the effect of UV photofunctionalization technology on the characteristics of titanium surfaces, biological activity and implant osseointegration, as well as its current clinical applications. Studies have shown that the superhydrophilicity of the titanium surface and improved biological activity endowed by UV photofunctionalization can accelerate and enhance bone formation, resulting in a higher success rate of implant surgery. Therefore, UV photofunctionalization has great potential for clinical chairside applications.
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O melanoma é um tipo de câncer de pele geneticamente diverso, que surge diante das transformações em melanócitos. A mutação BRAFV600E está presente em mais de 90% de todas as mutações em BRAF, sendo assim ocorre em cerca de 50% dos casos registrados. As mutações em NRAS, ocupam o segundo lugar entre as mutações mais prevalentes, cerca de 20% dos casos. Informações sobre as assinaturas genéticas, permitiram o desenvolvimento de terapia alvo dirigida. O Vemurafenib, inibidor da quinase BRAFV600E, apresentou inicialmente resultados bastante satisfatórios, contudo existe registro de casos de recidiva e resistência. O receptor aril de hidrocarbonetos é expresso em vários componentes da pele, e assim está relacionado a homeostase e fisiopatologia da pele. Diante disso, a avaliação da expressão do receptor em um painel de linhagens mutadas para NRAS e BRAF, e BRAF resistentes, mostrou-se maior do que a encontrada em melanócitos. Também encontramos maior expressão de mRNA de AhR em linhagens de melanoma derivadas de sítio primário e metastático, mutadas para BRAFV600E, quando comparadas ao melanócito. Agregado a isto, a análise in silico no TCGA (The Cancer Genome Atlas) mostrou que há 18% de alteração genética em AhR, sendo em maior parte a alta regulação de mRNA. Também, a análise do banco público GSE12391, mostrou aumento de mRNA de AhR na fase de crescimento vertical do melanoma. Assim, concluímos que há maior expressão de mRNA e sua importância nas fases de desenvolvimento do melanoma, tanto nos processos iniciais quanto em processos de migração, invasão e metástase. Ainda, encontramos maior mRNA do receptor em linhagens resistentes ao Vemurafenib. Este resultado sustenta a hipótese de que AhR pode ser considerado um marcador de resistência em melanomas. O AhR, inicialmente no citoplasma, quando ativado pode atuar como fator de transcrição regulando vários genes que apresentam sequências definidas, participando de respostas carcinogênicas. Compostos halogenados e moléculas endógenas derivadas das vias de metabolização do triptofano são agonistas do receptor. Anteriormente, nosso grupo mostrou que linhagens de melanoma incubadas com triptamina e DMT exibiram menor clonogenicidade. Diante de uma literatura escassa sobre o papel do DMT no melanoma e com base nestes resultados, nosso objetivo foi avaliar o papel de AhR nesta interface DMT-melanoma. Para isto, nosso objetivo foi construir linhagem editada geneticamente para AhR através da ferramenta CRISPR-Cas9. Vários foram os esforços, sem sucesso, utilizados nas tentativas de comprovar a manutenção de células editadas na cultura. Atrelamos a este resultado a possibilidade de haver duas subpopulações editadas geneticamente pós CRISPR-Cas9, onde uma destas manteve o padrão de crescimento semelhante às células wild type. Devido a este crescimento diferencial, não obtivemos congruências nos ensaios e postulamos a perda do possível nocaute. A partir disso, realizamos ensaios de interactoma para avaliar a interação de DMT-AhR. Nosso resultado sugere a interação de DMT ao receptor sigma 1, e não ao receptor aril de hidrocarbonetos. Desta forma, o interactoma sustenta a hipótese de que DMT não é um ligante de AhR. Para certificar este resultado análises de docking associados a ensaios biológicos, avaliando o papel do receptor, devem ser realizados para averiguar a afinidade e seletividade de DMT como ligante do receptor na linhagem de melanoma
Melanoma is a genetically diverse type of skin cancer, which arises from changes in melanocytes. The BRAFV600E mutation is present in more than 90% of all BRAF mutations, so it occurs in about 50% of registered cases. Mutations in NRAS occupy the second place among the most prevalent mutations, about 20% of cases. Information on genetic signatures allowed the development of targeted therapy. vemurafenib, kinase inhibitor BRAFV600E, initially presented very satisfactory results, however there is a record of cases of relapse and resistance. The aryl hydrocarbon receptor is expressed in several components of the skin and is thus related to homeostasis and skin pathophysiology. Therefore, the evaluation of receptor expression in a panel of strains mutated to NRAS and BRAF, and resistant BRAF, proved to be greater than that found in melanocytes. We also found main expression of AhR mRNA in melanoma strains derived from primary and metastatic site, mutated to BRAFV600E, when compared to melanocyte. Added to this, the in silico analysis in TCGA (The Cancer Genome Atlas) showed that there is 18% of genetic alteration in AhR, being mostly the high regulation of mRNA. Also, an analysis by the public bank GSE12391, showed an increase in AhR mRNA in the vertical growth phase of melanoma. Thus, it is concluded that there is greater expression of mRNA and its importance in the stages of development of melanoma, both in recent processes and in the processes of migration, invasion and metastasis. In addition, we found higher receptor mRNA in strains resistant to vemurafenib. This result supports the hypothesis that AhR can be considered a marker of resistance in melanomas. AhR, initially in the cytoplasm, when activated can act as a transcription factor regulating several genes that have defined sequences, participating in carcinogenic responses. Along with this, we show that along the tumor progression, there is an increase in AhR in the radial growth phase of melanoma. Halogenated compounds and endogenous molecules derived from the tryptophan metabolism pathways are receptor agonists. Previously, our group showed that melanoma strains incubated with tryptamine and DMT exhibited less clonogenicity. In view of a scarce literature on the role of DMT in melanoma and based on these results, our objective was to evaluate the role of AhR in this DMT-melanoma interface. For this, our goal was to build genetically edited strain for AhR using the CRISPR-Cas9 tool. Several efforts were unsuccessful in attempts to prove the maintenance of cells edited in the culture. We linked to this result the possibility of having two subpopulations genetically edited after CRISPR-Cas9, where one of them maintained the growth pattern like wild type cells. Due to this differential growth, we did not obtain congruence in the tests and postulated the loss of the possible knockout. From that, we performed interactome assays to evaluate the DMT-AhR interaction. Our result suggests the interaction of DMT with the sigma 1 receptor, and not the aryl hydrocarbon receptor. Thus, the interactome supports the hypothesis that DMT is not an AhR ligand. To certify this result, docking analyses associated with biological assays, evaluating the role of the receptor, should be performed to ascertain the affinity and selectivity of DMT as a ligand of the receptor in the melanoma lineage
Subject(s)
Skin/injuries , Genome , Receptors, Aryl Hydrocarbon , Melanocytes/classification , Melanoma , Neoplasms/pathology , Phosphotransferases/antagonists & inhibitors , Association , Transcription Factors/agonists , Cytoplasm/classification , Human MigrationABSTRACT
La neumonía lipoidea es una enfermedad respiratoria poco conocida que resulta de la acumulación de lípidos de origen endógeno o exógeno a nivel del alveolo pulmonar. Suele ser subdiagnosticada ya que la presentación clínica es inespecífica, por lo que suele confundirse con otras patologías broncopulmonares. Se presentó el caso de un paciente de 18 años antecedentes de aspiración accidental de combustible que seis horas después comenzó con fiebre, hemoptisis, tos y disnea. Se realizó radiografía de tórax donde se observó una neumonía en base derecha que unido al interrogatorio y a la realización de la broncoscopía confirmaron el diagnóstico de neumonía lipoidea. El paciente evolucionó favorablemente con el tratamiento(AU)
Lipoid pneumonia is a little known respiratory disease that results from the accumulation of lipids of endogenous or exogenous origin in the pulmonary alveolus. It is usually underdiagnosed since the clinical presentation is nonspecific, which is why it is often confused with other bronchopulmonary pathologies. We report the case of an 18-year-old patient with a history of accidental fuel aspiration, who ran fever six hours later, together with hemoptysis, cough, and dyspnea. Chest X-rays showed a right base pneumonia. The questioning and the performance of the bronchoscopy confirmed the diagnosis of lipoid pneumonia. The patient evolved favorably with the treatment(AU)
Subject(s)
Humans , Male , Adolescent , Pneumonia, Aspiration/drug therapy , Pneumonia, Lipid/diagnosis , Bronchoscopy/methods , Radiography, Thoracic/methodsABSTRACT
Objective:To investigate the effect of resveratrol on the expression of inflammatory cytokines and related genes in human SZ95 sebocytes induced by benzo (a) pyrene.Methods:Human SZ95 sebocytes were cultured in vitro, and divided into 4 groups: control group treated with 1‰ dimethyl sulfoxide for 27 hours, resveratrol group treated with 1 × 10 -5 mol/L resveratrol for 24 hours, benzo (a) pyrene group treated with 1 × 10 -5 mol/L benzo (a) pyrene for 3 hours, resveratrol+benzo (a) pyrene group treated with 1 × 10 -5 mol/L resveratrol for 24 hours followed by 1 × 10 -5 mol/L benzo (a) pyrene for 3 hours. Real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of interleukin (IL) -1α, IL-6, aryl hydrocarbon receptor (AhR) , cytochrome P4501A1 (CYP1A1) and cytochrome P4501B1 (CYP1B1) in SZ95 sebocytes in the above groups; Western blot analysis was conducted to determine the phosphorylation level of p38 mitogen-activated protein kinase (p38 MAPK, expressed as the ratio of phosphorylated to total p38 MAPK) and AhR protein expression; enzyme-linked immunosorbent assay (ELISA) was conducted to detect levels of IL-1α and IL-6 in the cell culture supernatant in each group. One-way analysis of variance was used for comparison of means among multiple groups, and least significant difference- t test was used for multiple comparisons. Results:The mRNA and protein expression of IL-1α in SZ95 sebocytes significantly differed among the control group, resveratrol group, benzo (a) pyrene group and resveratrol+benzo (a) pyrene group (mRNA: 2.045 ± 0.272, 2.058 ± 0.154, 3.124 ± 0.094, 2.185 ± 0.337, protein: 9.132 ± 1.181, 9.429 ± 0.771, 20.361 ± 0.907, 9.917 ± 0.897, F=14.662, 101.705, P < 0.01, < 0.001, respectively) , and were significantly lower in the resveratrol+benzo (a) pyrene group than in the benzo (a) pyrene group (both P < 0.01) . In addition, the phosphorylation level of p38 was significantly higher in the benzo (a) pyrene group than in the control group, resveratrol group and resveratrol+benzo (a) pyrene group ( F=303.129, P < 0.000 1) . The mRNA expression of AhR, CYP1A1 and CYP1B1 was significantly lower in the resveratrol+benzo (a) pyrene group than in the benzo (a) pyrene group ( t=10.64, 33.599, 18.327, respectively, all P < 0.001) . The benzo (a) pyrene group showed significantly decreased protein expression of AhR compared with the resveratrol+benzo (a) pyrene group ( P < 0.001) . Conclusion:Resveratrol can inhibit the environmental pollutant benzo (a) pyrene-induced expression of inflammatory factor IL-1α in SZ95 sebocytes, which is likely mediated by the AhR and p38MAPK pathways.
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OBJECTIVE Aryl hydrocarbon receptor (Ahr) is thought to be a crucial factor that regulates immune responses, which may be involved in the pathogenesis of autoimmune inflammation including rheumatoid arthritis (RA). The results of our group in recent years have shown that CP-25, a novel ester derivative of paeoniflorin, has a good effect on improving RA animal models. However, whether the anti-arthritis effect of CP-25 is related to Ahr remains unclear. METHODS CP-25 treatment ameliorated adjuvant-induced arthritis (AA), a mouse model of RA, by inhibiting Ahr-related activities in fibroblasts like synoviocytes (FLS). AA rats were treated with CP-25 or paroxetine from day 17 to 33 after immunization. RESULTS CP-25 alleviated arthritis symptoms and the pathological changes, decreased the expression of Ahr in the synovium and FLS of AA rats. Besides, treatment with CP-25 reduced the proliferation and migration of MH7A caused by Ahr activation. In addition, we also demonstrated that CP-25 down-regulated the co-expres?sion and co-localization of Ahr and G protein-coupled receptor kinase 2 (GRK2) in MH7A. CONCLUSION The data pre?sented here demonstrated that CP-25 suppressed FLS dysfunction in rats with AA, which were associated with reduced Ahr activation and the interaction between Ahr and GRK2.