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1.
Phys Chem Chem Phys ; 24(36): 21822-21832, 2022 Sep 21.
Article in English | MEDLINE | ID: mdl-36063116

ABSTRACT

Formation and stability of the B56 boron cluster were investigated using a topological approach and the disk aromaticity model. An extensive global energy minimum search for the B56 system which was carried out by means of the Mexican Enhanced Genetic Algorithm (MEGA) in conjunction with density functional theory computations, confirms a quasi-planar structure as its energetically most stable isomer. Such a structural motif is derived by applying a topological leapfrog operation to a B12 form. Its high thermodynamic stability can be explained by the disk aromaticity model in which the delocalization of its π orbitals can be assigned to the levels of a particle in a circular box with the [(1σ)2 (1π)4 (1δ)4 (1φ)4 (2σ)2 (1γ)4 (2π)4 (2δ)4 (1η)4 (2φ)4 (1θ)2] electronic configuration. This π delocalization is confirmed by other delocalization indices. While the B56 has a similar electron delocalization to that of the quasi-planar B50, they have opposite magnetic ring current properties because of the symmetry selection rules of their HOMO-LUMO electronic transitions. The π delocalization in the boron clusters is larger at long distances as compared to carbon clusters at similar sizes, but such a trend is reversed at shorter distances.

2.
Plant Dis ; 105(6): 1748-1757, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33206018

ABSTRACT

Pseudomonas syringae pv. actinidiae is the etiological agent of kiwifruit canker disease, causing severe economic losses in kiwifruit production areas around the world. Rapid diagnosis, understanding of bacterial virulence, and rate of infection in kiwifruit cultivars are important in applying effective measures of disease control. P. syringae pv. actinidiae load in kiwifruit is currently determined by a labor-intense colony counting method with no high-throughput and specific quantification method being validated. In this work, we used three alternative P. syringae pv. actinidiae quantification methods in two infected kiwifruit cultivars: start of growth time, quantitative PCR (qPCR), and droplet digital PCR (ddPCR). Method performance in each case was compared with the colony counting method. Methods were validated using calibration curves obtained with serial dilutions of P. syringae pv. actinidiae biovar 3 (Psa3) inoculum and standard growth curves obtained from kiwifruit samples infected with Psa3 inoculum. All three alternative methods showed high correlation (r > 0.85) with the colony counting method. qPCR and ddPCR were very specific, sensitive (5 × 102 CFU/cm2), highly correlated to each other (r = 0.955), and flexible, allowing for sample storage. The inclusion of a kiwifruit biomass marker increased the methods' accuracy. The qPCR method was efficient and allowed for high-throughput processing, and the ddPCR method showed highly accurate results but was more expensive and time consuming. While not ideal for high-throughput processing, ddPCR was useful in developing accurate standard curves for the qPCR method. The combination of the two methods is high-throughput, specific for Psa3 quantification, and useful for research studies (e.g., disease phenotyping and host-pathogen interactions).


Subject(s)
Actinidia , Pseudomonas syringae , Fruit , Plant Diseases , Pseudomonas syringae/genetics , Real-Time Polymerase Chain Reaction
3.
Plant Cell ; 27(3): 772-86, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25724639

ABSTRACT

Ascorbate (vitamin C) is an essential antioxidant and enzyme cofactor in both plants and animals. Ascorbate concentration is tightly regulated in plants, partly to respond to stress. Here, we demonstrate that ascorbate concentrations are determined via the posttranscriptional repression of GDP-l-galactose phosphorylase (GGP), a major control enzyme in the ascorbate biosynthesis pathway. This regulation requires a cis-acting upstream open reading frame (uORF) that represses the translation of the downstream GGP open reading frame under high ascorbate concentration. Disruption of this uORF stops the ascorbate feedback regulation of translation and results in increased ascorbate concentrations in leaves. The uORF is predicted to initiate at a noncanonical codon (ACG rather than AUG) and encode a 60- to 65-residue peptide. Analysis of ribosome protection data from Arabidopsis thaliana showed colocation of high levels of ribosomes with both the uORF and the main coding sequence of GGP. Together, our data indicate that the noncanonical uORF is translated and encodes a peptide that functions in the ascorbate inhibition of translation. This posttranslational regulation of ascorbate is likely an ancient mechanism of control as the uORF is conserved in GGP genes from mosses to angiosperms.


Subject(s)
Arabidopsis/genetics , Ascorbic Acid/biosynthesis , Feedback, Physiological , Gene Expression Regulation, Plant , Open Reading Frames/genetics , 5' Untranslated Regions/genetics , Amino Acid Sequence , Arabidopsis/drug effects , Ascorbic Acid/pharmacology , Biosynthetic Pathways/drug effects , Codon/genetics , Down-Regulation/drug effects , Feedback, Physiological/drug effects , Galactose/metabolism , Gene Expression Regulation, Plant/drug effects , Luciferases/metabolism , Molecular Sequence Data , Peptides/chemistry , Phosphotransferases/metabolism , Plant Leaves/drug effects , Plant Leaves/metabolism , Promoter Regions, Genetic/genetics , Protein Biosynthesis/drug effects , Ribosomes/drug effects , Ribosomes/metabolism
4.
Front Plant Sci ; 15: 1408202, 2024.
Article in English | MEDLINE | ID: mdl-38966143

ABSTRACT

Pepino (Solanum muricatum) is an herbaceous crop phylogenetically related to tomato and potato. Pepino fruit vary in color, size and shape, and are eaten fresh. In this study, we use pepino as a fruit model to understand the transcriptional regulatory mechanisms controlling fruit quality. To identify the key genes involved in anthocyanin biosynthesis in pepino, two genotypes were studied that contrasted in foliar and fruit pigmentation. Anthocyanin profiles were analyzed, as well as the expression of genes that encode enzymes for anthocyanin biosynthesis and transcriptional regulators using both RNA-seq and quantitative PCR. The differential expression of the transcription factor genes R2R3 MYB SmuMYB113 and R3MYB SmuATV suggested their association with purple skin and foliage phenotype. Functional analysis of these genes in both tobacco and pepino showed that SmuMYB113 activates anthocyanins, while SmuATV suppresses anthocyanin accumulation. However, despite elevated expression in all tissues, SmuMYB113 does not significantly elevate flesh pigmentation, suggesting a strong repressive background in fruit flesh tissue. These results will aid understanding of the differential regulation controlling fruit quality aspects between skin and flesh in other fruiting species.

5.
Indian J Nephrol ; 34(1): 56-58, 2024.
Article in English | MEDLINE | ID: mdl-38645920

ABSTRACT

Introduction: Coronavirus disease 2019 (COVID-19) induces organic damage mainly through the patient's immune overreaction. Hemoperfusion (HPF) can remove inflammatory cytokines and can reduce the negative effects of cytokine storm in COVID-19. We compared the mortality rate, inflammatory response, and acute kidney injury (AKI) prevalence among patients suffering from respiratory insufficiency secondary to COVID-19 treated with and without HPF with HA330 cartridge. Methods: Mortality rate, serum creatinine, and ferritin values were compared between patients suffering from respiratory insufficiency secondary to COVID-19 who received conventional treatment and another group of patients who additionally received four sessions of HPF with HA330. Results: Of 116 patients suffering from acute respiratory insufficiency secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), one group (n: 84) received support treatment and the other group (n: 32) additionally received HPF with HA330 cartridge. Both groups had no renal disease and similar age and comorbidities at admission, except for obesity and mechanical ventilation requirement, which were significantly higher in the HPF group. Mortality rate (61% vs. 31%, P: 0.008), serum creatinine (1.4 vs. 0.5 mg/dl, P < 0.001), and post-HPF serum ferritin (2868 vs. 1675, P < 0.001) were significantly lower in the HPF group. Conclusion: Mortality rate, serum ferritin, and AKI were significantly reduced in critical COVID-19 patients who received HPF with HA330 cartridge than in those who did not receive it. These results were obtained despite the HPF group risk factors, such as obesity and mechanical ventilation, worsening its prognosis.

6.
J Pers Med ; 14(5)2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38793049

ABSTRACT

The article discusses the importance of accurately distinguishing HER2-low from HER2-negative breast cancer, as novel ADCs have demonstrated activity in a large population of patients with HER2-low-expressing BC. While current guidelines recommend a dichotomous classification of HER2 as either positive or negative, the emergence of the HER2-low concept calls for standardization of HER2 testing in breast cancer, using currently available assays to better discriminate HER2 levels. This review covers the evolution and latest updates of the ASCO/CAP guidelines relevant to this important biomarker in breast cancer, including still-evolving concepts such as HER2 low, HER2 heterogeneity, and HER2 evolution. Our group presents the latest Mexican recommendations for HER2 status evaluation in breast cancer, considering the ASCO/CAP guidelines and introducing the HER2-low concept. In the era of personalized medicine, accurate HER2 status assessment remains one of the most important biomarkers in breast cancer, and the commitment of Mexican pathologists to theragnostic biomarker quality is crucial for providing the most efficient care in oncology.

7.
ChemMedChem ; 18(20): e202300184, 2023 10 17.
Article in English | MEDLINE | ID: mdl-37642254

ABSTRACT

In this work, a new set of quinazolin-2,4,6-triamine derivatives were synthesized to explore their potential biological activity as xanthine oxidase (XO) inhibitors, superoxide scavengers and screening of their toxicological profile. Among all the synthesized compounds, B1 exhibited better inhibitory activity against bovine xanthine oxidase (bXO) than allopurinol (IC50 =1.56 µM and IC50 =6.99 µM, respectively). As superoxide scavengers, B1, B2 and B13 exhibited a better effect than allopurinol (97.3 %, 82.1 %, 87.4 % and 69.4 %, respectively). Regarding the toxicological profile, B1 was less cytotoxic than methotrexate on HCT-15 cancer cells. Apoptosis results obtained in cells of female and male mice, showed that B1 and B2 presented a similar behaviour to CrO3 (positive control) with respect to the average frequency to induce apoptosis; while B13 apoptosis induced effect was similar to DMSO and control group. Finally, B1, B2, B13 did not induce genotoxicity in a micronuclei murine model compared to CrO3 .


Subject(s)
Allopurinol , Xanthine Oxidase , Female , Male , Animals , Cattle , Mice , Allopurinol/pharmacology , Superoxides , Enzyme Inhibitors/toxicity , Pyrazoles/pharmacology
8.
Neotrop Entomol ; 52(5): 837-847, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37552457

ABSTRACT

Mountain ecosystems experience abrupt abiotic changes that represent environmental filters for many organisms, shaping their phenotypic expressions. However, little is known about the morphological and symmetric adjustments of native bees along altitudinal gradients. We evaluated the changes on wing morphology, wing size, and vein fluctuating asymmetry (FA) of Eulaema nigrita Lepeletier (Apidae: Euglossini) associated with climatic variables along an altitudinal gradient in the rupestrian grassland (known also as campo rupestre or rupestrian field) of Serra do Cipó, Brazil. Seven sampling points along the altitudinal gradient were selected and distributed among 800 and 1400 m.a.s.l., and then, 40 individuals of E. nigrita were collected per each altitudinal point to determine the FA levels and the morphological changes using geometric morphometric techniques. We found that the wing size of E. nigrita decreased with increasing altitude. At the highest altitudes, the levels of FA of the wing veins were greater compared to bees from lower altitudes. We detected significant changes in wing morphology along the altitudinal gradient; bees of lower altitudes showed longer and wider wings than bees of higher altitudes, which had narrower and less elongated wings. Our results show a set of morphological adjustments and phenotypic expressions in E. nigrita associated with the variation in environmental conditions along the altitudinal gradient. We highlight the importance of environmental variables as insect-stressor factors, and that FA and geometric morphometric can be excellent tools for monitoring and evaluating environmental stresses.


Subject(s)
Ecosystem , Grassland , Humans , Bees , Animals , Brazil , Altitude , Phenotype
9.
Sci Rep ; 12(1): 3487, 2022 03 03.
Article in English | MEDLINE | ID: mdl-35241744

ABSTRACT

Monitoring the progression of SARS-CoV-2 outbreaks requires accurate estimation of the unobservable fraction of the population infected over time in addition to the observed numbers of COVID-19 cases, as the latter present a distorted view of the pandemic due to changes in test frequency and coverage over time. The objective of this report is to describe and illustrate an approach that produces representative estimates of the unobservable cumulative incidence of infection by scaling the daily concentrations of SARS-CoV-2 RNA in wastewater from the consistent population contribution of fecal material to the sewage collection system.


Subject(s)
COVID-19/epidemiology , SARS-CoV-2/isolation & purification , Wastewater/virology , COVID-19/virology , Humans , Incidence
10.
Nutrition ; 99-100: 111650, 2022.
Article in English | MEDLINE | ID: mdl-35468347

ABSTRACT

Globally, the prevalence of overweight and obesity, including among pregnant women, has substantially increased in the past three decades. This has been fueled by, among other factors, an increase in the consumption of high energy-dense foods and a decrease in physical activity. Additionally, global prevalence of anemia among pregnant women remains a public health concern. Overweight/obesity as well as anemia in pregnancy are independently associated with adverse health outcomes for the mother and offspring. In some pregnant women, the two conditions coexist. Yet current knowledge in this field, including prevalence rates, risk factors, and health consequences for mother and offspring being exposed to these conditions, is staggeringly sparse. In this review we describe the current evidence on prevalence rates, risk factors, and effects for mother and offspring regarding coexistence of overweight/obesity and anaemia in pregnant women based on a systematic literature search. We also highlight research gaps and suggest avenues for future research.


Subject(s)
Anemia , Overweight , Anemia/complications , Anemia/etiology , Female , Humans , Obesity/complications , Obesity/epidemiology , Overweight/complications , Overweight/epidemiology , Pregnancy , Prevalence , Risk Factors
11.
Photodiagnosis Photodyn Ther ; 37: 102630, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34798347

ABSTRACT

Reconstituted high-density lipoprotein (rHDL) nanoparticles are excellent transporters of molecules and very useful for targeted therapy as they specifically recognize the scavenger receptor, class B1 (SR-B1) that is present on the surface of a wide range of tumor cells. However, they have rarely been employed to transport photosensitizers (PS) for photodynamic therapy (PDT). Rhodamine (R) compounds have been dismissed as useful PSs for PDT due to their low 1O2 production, excitation wavelengths with little tissue penetration, and poor selectivity for tumor cells. It was recently demonstrated that when irradiating at 532 nm or with Cerenkov radiation (CR) from a ß-emitting radionuclide, R123, R6G, and RB undergo electron transfer reactions (type I reaction) with folic acid. R6G also produces type I reactions with O2. In this work, the photodynamic effects of the rHDL-R system were evaluated in vitro. rHDL nanoparticles loaded with R123, R6G, and RB were synthesized, and the PS was internalized into T47D tumor cells. When cells were irradiated with a 532-nm laser in the presence of an rHDL-R systems, a cytotoxic photodynamic effect was obtained in the order R6G > R123 > RB. In the presence of CR from a 177Lu source, cytotoxicity showed the order R6G > RB > R123. The higher cytotoxicity induced by R6G in both cases corresponds to higher cellular internalization and larger production of type I and II reactions. Thus, in this work, it is proposed that rHDL-R/177Lu system can be applied in theragnostics as a multimodal radiotherapy-PDT-imaging system (imaging by SPECT or Cerenkov) and in hypoxic solid tumors in which external radiation is not effective and 177Lu-CR acts as light source.


Subject(s)
Nanoparticles , Photochemotherapy , Cell Line, Tumor , Humans , Lipoproteins, HDL , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Rhodamines
12.
FEMS Microbes ; 2: xtab022, 2021.
Article in English | MEDLINE | ID: mdl-35128418

ABSTRACT

We assessed the relationship between municipality COVID-19 case rates and SARS-CoV-2 concentrations in the primary sludge of corresponding wastewater treatment facilities. Over 1700 daily primary sludge samples were collected from six wastewater treatment facilities with catchments serving 18 cities and towns in the State of Connecticut, USA. Samples were analyzed for SARS-CoV-2 RNA concentrations during a 10 month time period that overlapped with October 2020 and winter/spring 2021 COVID-19 outbreaks in each municipality. We fit lagged regression models to estimate reported case rates in the six municipalities from SARS-CoV-2 RNA concentrations collected daily from corresponding wastewater treatment facilities. Results demonstrate the ability of SARS-CoV-2 RNA concentrations in primary sludge to estimate COVID-19 reported case rates across treatment facilities and wastewater catchments, with coverage probabilities ranging from 0.94 to 0.96. Lags of 0 to 1 days resulted in the greatest predictive power for the model. Leave-one-out cross validation suggests that the model can be broadly applied to wastewater catchments that range in more than one order of magnitude in population served. The close relationship between case rates and SARS-CoV-2 concentrations demonstrates the utility of using primary sludge samples for monitoring COVID-19 outbreak dynamics. Estimating case rates from wastewater data can be useful in locations with limited testing availability, testing disparities, or delays in individual COVID-19 testing programs.

13.
Front Oncol ; 11: 660943, 2021.
Article in English | MEDLINE | ID: mdl-34094953

ABSTRACT

Cancer is a complex group of diseases that constitute the second largest cause of mortality worldwide. The development of new drugs for treating this disease is a long and costly process, from the discovery of the molecule through testing in phase III clinical trials, a process during which most candidate molecules fail. The use of drugs currently employed for the management of other diseases (drug repurposing) represents an alternative for developing new medical treatments. Repurposing existing drugs is, in principle, cheaper and faster than developing new drugs. Antihypertensive drugs, primarily belonging to the pharmacological categories of angiotensin-converting enzyme inhibitors, angiotensin II receptors, direct aldosterone antagonists, ß-blockers and calcium channel blockers, are commonly prescribed and have well-known safety profiles. Additionally, some of these drugs have exhibited pharmacological properties useful for the treatment of cancer, rendering them candidates for drug repurposing. In this review, we examine the preclinical and clinical evidence for utilizing antihypertensive agents in the treatment of cancer.

14.
BMJ Open ; 11(10): e051400, 2021 10 12.
Article in English | MEDLINE | ID: mdl-34642196

ABSTRACT

INTRODUCTION: The prevalence of childhood obesity has risen dramatically in recent years. A proportion of this burden has been attributed to factors that occur during the first 1000 days of life such as genetic predisposition, breast feeding and complementary feeding. Although the mechanisms by which these factors affect weight and adiposity are less well understood, appetite and satiety regulation may be a key to understanding them. This cohort study aims to investigate the role of appetite and satiety regulation as a mediator in the association between infant feeding practices and genetic polymorphisms with children's growth, adiposity and metabolic risk factors. METHODS AND ANALYSIS: 'MAS-Lactancia' (the first word means 'more' and is also an acronym in Spanish for 'Appetite and Satiety Mechanisms', the second word is 'breastfeeding') is an open, ongoing, prospective birth cohort that began the enrolment in 2016 of mother-child pairs affiliated to the Mexican Social Security Institute and that live in the city of Cuernavaca, Mexico. Pregnant women between 16-week and 22-week gestation are followed during the second half of their pregnancies, at birth and throughout their infant's first 48 months of life (at 1 month, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months, 36 months and 48 months) at the clinic and at-home visits that include questionnaires, anthropometric measurements and biospecimen collection. The main exposure variables are infant feeding (breast feeding and complementary feeding) and genetic polymorphisms (fat mass and obesity-associated, leptin and adiponectin genes). Outcome variables include infant's growth, adiposity and metabolic risk factors. We will conduct longitudinal models and path analyses to identify the potential mediating role of satiety and appetite indicators (leptin, adiponectin, insulin concentrations, appetite and satiety perception). ETHICS AND DISSEMINATION: The study protocol, data collection instruments, consent forms and procedures were approved by the institutional review boards of the National Institute of Public Health and the Mexican Social Security Institute in Mexico. Findings will be disseminated through conferences, peer-reviewed publications and meetings with stakeholders.


Subject(s)
Appetite , Pediatric Obesity , Adiposity , Breast Feeding , Child , Cohort Studies , Female , Humans , Infant , Infant, Newborn , Pediatric Obesity/epidemiology , Pediatric Obesity/genetics , Pregnancy , Prospective Studies
15.
Infez Med ; 28(1): 82-86, 2020 Mar 01.
Article in English | MEDLINE | ID: mdl-32172265

ABSTRACT

Tuberculous meningitis (TBM) is a medical emergency: it is the most severe, lethal and disabling clinical form of tuberculosis. We report the case of a 44-year-old woman who had undergone a clandestine abortion six weeks before admission. One week later, she had abnormal vaginal discharge. Three weeks prior to admission, headache, hyperpyrexia and mental alteration were added. At admission, a transvaginal ultrasound showed abnormalities of the uterine cavity. Sepsis and endometritis were diagnosed, and a hysterectomy was scheduled. During preoperative evaluation, meningeal signs were found. The first lumbar puncture (LP) showed a lymphomononuclear pleocytosis, hypoglycorrhachia and hyperproteinorrachia. After five days treatment with ceftriaxone, vancomycin and dexamethasone, only partial recovery occurred. A second LP showed AFB and PCR confirmed Mycobacterium tuberculosis. The histopathology of endometrial biopsy confirmed endometrial tuberculosis. Therapeutic response to anti-tuberculous treatment and corticosteroids was excellent. No other cause of immunosuppression apart from pregnancy was found. To the best of our knowledge, this is the first report of TBM secondary to endometrial tuberculosis and highlights an unusual clinical scenario in which severe and disseminated forms of TB could be present. TBM during and after pregnancy is rare, but compared with TBM in non-pregnant women, it has a poorer prognosis. Early diagnosis and treatment can be lifesaving in this life-threatening disease.


Subject(s)
Abortion, Criminal/adverse effects , Mycobacterium tuberculosis/isolation & purification , Tuberculosis, Female Genital/complications , Tuberculosis, Meningeal/etiology , Uterine Diseases/complications , Adult , Female , Humans , Pregnancy , Tuberculosis, Female Genital/drug therapy , Tuberculosis, Meningeal/drug therapy , Uterine Diseases/drug therapy
16.
BMC Cell Biol ; 10: 77, 2009 Oct 30.
Article in English | MEDLINE | ID: mdl-19878551

ABSTRACT

BACKGROUND: A significant percentage of patients with pancreatitis often presents a history of excessive alcohol consumption. Nevertheless, the patho-physiological effect of ethanol on pancreatitis remains poorly understood. In the present study, we have investigated the early effects of acute ethanol exposure on CCK-8-evoked Ca2+ signals in mouse pancreatic acinar cells. Changes in [Ca2+]i and ROS production were analyzed employing fluorescence techniques after loading cells with fura-2 or CM-H2DCFDA, respectively. RESULTS: Ethanol, in the concentration range from 1 to 50 mM, evoked an oscillatory pattern in [Ca2+]i. In addition, ethanol evoked reactive oxygen species generation (ROS) production. Stimulation of cells with 1 nM or 20 pM CCK-8, respectively led to a transient change and oscillations in [Ca2+]i. In the presence of ethanol a transformation of 20 pM CCK-8-evoked physiological oscillations into a single transient increase in [Ca2+]i in the majority of cells was observed. Whereas, in response to 1 nM CCK-8, the total Ca2+ mobilization was significantly increased by ethanol pre-treatment. Preincubation of cells with 1 mM 4-MP, an inhibitor of alcohol dehydrogenase, or 10 microM of the antioxidant cinnamtannin B-1, reverted the effect of ethanol on total Ca2+ mobilization evoked by 1 nM CCK-8. Cinnamtannin B-1 blocked ethanol-evoked ROS production. CONCLUSION: ethanol may lead, either directly or through ROS generation, to an over stimulation of pancreatic acinar cells in response to CCK-8, resulting in a higher Ca2+ mobilization compared to normal conditions. The actions of ethanol on CCK-8-stimulation of cells create a situation potentially leading to Ca2+ overload, which is a common pathological precursor that mediates pancreatitis.


Subject(s)
Calcium/metabolism , Ethanol/pharmacology , Pancreas, Exocrine/metabolism , Sincalide/pharmacology , Alcohol Dehydrogenase/metabolism , Animals , Anthocyanins/pharmacology , Antioxidants/pharmacology , Cells, Cultured , Fluorescent Dyes/chemistry , Fluorescent Dyes/metabolism , Fura-2/chemistry , Fura-2/metabolism , Homeostasis/drug effects , Male , Mice , Pancreas, Exocrine/cytology , Proanthocyanidins , Reactive Oxygen Species/metabolism , Time Factors
17.
Food Chem Toxicol ; 123: 151-161, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30393115

ABSTRACT

Hexachlorobenzene (HCB) is a dioxin-like compound widely distributed and is a weak ligand of the aryl hydrocarbon receptor (AhR). Endometriosis is a disease characterized by growth of endometrial tissue in ectopic sites. Our aim was to investigate the impact of HCB on the endocrine, invasion and inflammatory parameters in a rat endometriosis model surgically induced. Female rats were exposed to HCB (1, 10 and 100 mg/kg b.w.) during 30 days. Results showed that HCB increases endometriotic like-lesions (L) volume in a dose-dependent manner. In L, HCB10 increases microvessel density (immunohistochemistry) and the vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) and AhR levels (Western Blot), while HCB1 enhances aromatase expression (Western Blot). In addition, in eutopic endometrium (EU), HCB10/HCB100 augments microvessel density, VEGF and MMP-9 expression, while HCB1/HCB10 increases tumor necrosis factor-α (TNF-α) content in peritoneal fluid (ELISA). Interestingly, both L and EU from HCB-treated rats exhibited higher estrogen receptor α (ERα) (immunohistochemistry) and metalloproteases (MMP)-2 and -9 levels (Western Blot), as well as lower progesterone receptor (PR) expression (immunohistochemistry) than in control rats. Environmentally relevant concentrations of HCB could contribute to abnormal changes associated with endometriosis progression and development.


Subject(s)
Endometriosis/etiology , Endometriosis/metabolism , Environmental Exposure/adverse effects , Hexachlorobenzene/adverse effects , Animals , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Disease Progression , Endometriosis/genetics , Endometriosis/pathology , Environmental Exposure/analysis , Environmental Pollutants/adverse effects , Environmental Pollutants/analysis , Estrogen Receptor alpha/genetics , Estrogen Receptor alpha/metabolism , Female , Hexachlorobenzene/analysis , Humans , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism
18.
Toxicol Lett ; 177(2): 116-22, 2008 Mar 15.
Article in English | MEDLINE | ID: mdl-18295415

ABSTRACT

Hexachlorobenzene (HCB) is a widespread environmental pollutant. It has some properties that are typical for dioxin-like compounds that act mainly through the aryl hydrocarbon receptor (AhR) protein. Upon dioxin binding, the AhR translocates to the nucleus and modulates gene expression. At the same time, c-Src kinase frees from the AhR complex and thereby activates its own kinase activity, which acts as a trigger for the growth factor receptor signal transduction pathway. HCB is a weak agonist of the AhR, and the evidence that HCB toxicity is mediated via the AhR complex is limited and inconclusive. In the present study, female Wistar rats were administered HCB (1, 10 and 100mg/kg) for 30 days. Liver cytosolic AhR was translocated to the nucleus. The activity of liver microsomal c-Src increased at all assayed doses. HCB induced the association of the EGFR with c-Src and increased the phosphorylation of EGFR at tyrosine 845 (Tyr845), a known c-Src phosphorylation site. c-Src from WB-F344 cells treated with HCB exhibited increased protein levels and c-Src-pTyr416 phosphorylation than the control cells. Again HCB induced EGFR phosphorylation at Tyr845. Such an effect of HCB could not be detected when c-Src activity was blocked by PP2. All together, our data demonstrates that HCB may induce EGFR transactivation through an c-Src-dependent pathway.


Subject(s)
Environmental Pollutants/toxicity , Fungicides, Industrial/toxicity , Hexachlorobenzene/toxicity , Liver/drug effects , Receptors, Aryl Hydrocarbon/metabolism , Animals , CSK Tyrosine-Protein Kinase , Cell Nucleus/drug effects , Cells, Cultured , Enzyme Activation , ErbB Receptors/metabolism , Female , Liver/metabolism , Phosphorylation/drug effects , Protein Transport/drug effects , Protein-Tyrosine Kinases/metabolism , Rats , Rats, Wistar , Transcriptional Activation/drug effects , src-Family Kinases
19.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1398377

ABSTRACT

Introducción: Los linfomas gástricos primarios representan menos del 5% de los linfomas no Hodgkin (LNH). La gran mayoría de linfomas gástricos primarios son linfomas de células B de alto grado. Los linfomas gástricos primarios de células T son muy raros y usualmente se asocian a infección por HTLV-1 en regiones endémicas. Material y método. Describimos el caso de una paciente mujer de mediana edad que se presentó con neumoperitoneo debido a ulcera gástrica perforada, síndrome consuntivo y lesiones cutáneas y orales. Resultados. La histopatología e inmunohistoquímica confirmaron linfoma gástrico primario de células T con compromiso cutáneo. La serología para HTLV-1, virus del Epstein-Barr y VIH fueron negativas. Conclusión. La finalidad de este reporte es dar a conocer esta forma de presentación sumamente rara de linfoma gástrico primario.


Background: Primary gastric lymphomas account for less than5%ofnon-Hodgkinlymphomas(NHL).Thevast majority of primary gastric lymphomas are high-grade B-cell lymphomas. Primary gastric T-cell lymphomas are very rare and are usually associated with HTLV-1 infection in endemic regions. We describe Material and methods.the case of a middle-aged female patient who presented with pneumoperitoneum due to a perforated gastric ulcer, wasting syndrome, and skin and oral lesions. . Results: Histopathology and immunohistochemistry confirmed primary gastric T-cell lymphoma with skin involvement. The serologyfor HTLV-1,Epstein-Barr virus and HIVwere negative. The aim of this report is to present Conclusion: this extremely rare presentation of primary gastric lymphoma

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