RESUMEN
Aluminum is a key component in nearly nourishment stuffs and medications. It is also found in treated drinking water in the form of reactive species, and aluminum salts are commonly utilized as flocculants in water treatment. Meanwhile, it was not thought to be a dangerous metal for people, but research showed a possible link with Alzheimer's disease, breast cancer, autism, and aluminum. Controlling the amount of aluminum in food processing, agriculture, and drinking water is crucial, thus newly synthesized Al(III) ion selective electrode based on innocuous reagent, flubendazole drug, has been developed. The electrode displayed Nernstian slopes of 20.11 0.47 mV decade-1 at 25 ± 1 °C, covering a wide concentration range of Al(III) from 1 × 10-7 to 1 × 10-1 mol L-1. The response mechanism is studied using IR, computational calculations, morphological tools. The developed sensor has been utilized to accurately measure Al(III) ions in genuine water samples, multivitamin syrup, and food stuff.
Asunto(s)
Carbono , Agua Potable , Humanos , Aluminio/análisis , Teoría Funcional de la DensidadRESUMEN
The biodiversity of the agroecosystem leads to changes in the Floristic composition, diversity, and abundance of weed species in crop and orchard farms. The present study is considered the first attempt to categorize, evaluate, and document the diversity of weed populations among different grape farms in Tayma, Tabuk region, Saudi Arabia. The results of ANOVA showed that the number of weed species varied significantly across the six grape farms. During six grape farms under study, 30 weed species belonging to thirteen families and 28 genera were recorded. In total, twelve weed species belong to the Poaceae family with a rate of 40%. While the other families are represented either by one or two species with rates of 3.3% and 6.7%, respectively. Biogeographic origins analysis showed that the Tropical area represented 23.3% of total weed flora, followed by Saharo Arabian (16.7%), Mediterannean-Euro Siberian-Irano-Turanian (13.3%) and American (10.0%). Therophytes were the dominant life forms with a rate of 66.7%, followed by Hemicryptophyte (20.0%), Geophyte (6.7%), and Chamaephyte (6.7%). A total of 16 and 14 weed species belong to the annual and perennial life span, respectively. Also, the grass and herb habits represented 40% and 60% of 30 weed species, respectively. According to the abundance score, the most common weed species of those grape farms in the region study are Cynodon dactylon, Desmostachya bipinnata, and Setaria verticillata, they belong to the Poaceae family. Based on the presence and absence of weed species in grape farms, the Principal Component Analyses (PCA) show that the grape farms and weed species (into two groups) are distinguished mainly along the first two components. Also, positive correlations were observed among most grape farms, according to PCA. Generally, more studies on the ecological aspects and floristic composition of weed species in grape farms are also needed.
RESUMEN
This research studied the enhancing effect on the nanofiltration composite (TFCNF) membrane of two non-ionic surfactants on a thin-film composite nanofiltration membrane (TFCNF) for calcite scale (CaCO3) inhibition in oilfield application to develop a multifunctional filtration system: nanofiltration, antiscalant, and scale inhibitors. The effectiveness of dodecyl phenol ethoxylate (DPE) and oleic acid ethoxylate (OAE) as novel scale inhibitors were studied using the dynamic method. Scaling tests on the membrane were performed to measure the scaling of the inhibited membrane with and without scale inhibitors for salt rejection, permeability, and flux decline. The results revealed that the TFCNF membrane flux decline was improved in the presence of scale inhibitors from 22% to about 15%. The rejection of the membrane scales increases from 72% for blank membranes, reaching 97.2% and 88% for both DPE and OAE, respectively. These confirmed that scale inhibitor DPE had superior anti-scaling properties against calcite deposits on TFCNF membranes. Inhibited scaled TFCNF membrane was characterized using environmental scanning electron (ESEM), FTIR, and XRD techniques. The results of the prepared TFCNF membrane extensively scaled by the calcite deposits were correlated to its morphology.
RESUMEN
The objective of this work was to investigate the effect of microfluidics on the quality attributes of metformin hydrochloride-loaded poly lactic-co-glycolic acid polymeric particles (MFH-PLGA PPs) when compared to a traditional double emulsion batch method. The relationship of encapsulation and loading efficiencies, yield %, particle size, surface morphology, and release profile with process and formulation variables were determined using design of experiments (DoE). The effects of the dispersal method of the primary (sonication vs. vortex) or secondary emulsion (microfluidics vs. batch), polyvinyl alcohol concentration (PVA), and drug to polymer ratio were investigated. The PPs' size was impacted by both the PVA concentration and the type of primary and secondary emulsion dispersion methods. Microfluidics significantly increased the PPs' yield %, particle size, encapsulation, and loading efficiencies. The higher loaded microfluidic-based PPs had more burst release, following first-order release kinetics when compared to the lower loaded batch-based particles, which followed the Korsmeyer-Peppas model for release kinetics. Microfluidic-based PPs exhibited a smooth, porous, more uniform, and larger particle size with hollow structure than the batch-based PPs with a matrix-like structure. In conclusion, we have elucidated the effect of microfluidics on the quality attributes of MFH-PLGA PPs and their comparison to the traditional batch technique.
Asunto(s)
Microfluídica , Polímeros , Portadores de Fármacos , Emulsiones , Microesferas , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido PoliglicólicoRESUMEN
No currently available treatment is able to generate new contractile tissue or significantly improve cardiac function after myocardial infarction (MI), a leading cause of morbidity and mortality worldwide. Although gene transfer-enhanced endothelial progenitor cells (GTE-EPCs) show effectiveness in MI treatment in small animal models, no clinical trials using GTE-EPCs have been documented. Before the introduction of GTE-EPCs into human trials, gene-transfer-mediated augmentation of EPC function in animal models that reflect the human MI scenario should be tested. In this regard, a porcine model is the best choice since pigs have cardiac size, hemodynamics and coronary anatomy similar to that of humans. To examine GTE-EPC therapeutic efficacy in pig MI models, an efficient method for gene transfer into pig EPCs is required, which however, has been poorly documented. Pig bone marrow mononuclear cells were isolated and cultured in EGM-2 medium to obtain bone marrow-derived EPCs (BM-EPCs) that were characterized by immunostaining and the tube formation assay. Gene transfer was optimized in 6-well plates using a GFP and a VEGF plasmid, and scaled up in T75 flasks. Gene transfer efficiency was determined by fluorescence microscopy and flow cytometry. VEGF levels were measured by ELISA. Cell proliferation was assayed by the CCK-8 kit. (1) BM-EPCs expressed VEGFR2 and eNOS but not CD45 protein, and formed tube structures on Matrigel; (2) several chemical compounds were explored with the highest transfection efficiency of 41.4% ± 5.8% achieved using Lipofectamine 3000; (3) the VEGF level in culture medium after VEGF transfection was 378 ± 48 ng/106 cells; and (4) BM-EPCs overexpressing VEGF had significantly enhanced proliferation than GFP-transfected EPCs. A simple, easy and cheap method that can be applied to produce a large number of genetically-modified BM-EPCs was established, which will facilitate the study of GTE-EPC therapeutic efficacy in pig MI model.
Asunto(s)
Células Progenitoras Endoteliales , Animales , Médula Ósea/metabolismo , Células Progenitoras Endoteliales/metabolismo , Técnicas de Transferencia de Gen , Porcinos , Transfección , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
At the liquid-gas phase transition in water, the density has a discontinuity at atmospheric pressure; however, the line of these first-order transitions defined by increasing the applied pressure terminates at the critical point1, a concept ubiquitous in statistical thermodynamics2. In correlated quantum materials, it was predicted3 and then confirmed experimentally4,5 that a critical point terminates the line of Mott metal-insulator transitions, which are also first-order with a discontinuous charge carrier density. In quantum spin systems, continuous quantum phase transitions6 have been controlled by pressure7,8, applied magnetic field9,10 and disorder11, but discontinuous quantum phase transitions have received less attention. The geometrically frustrated quantum antiferromagnet SrCu2(BO3)2 constitutes a near-exact realization of the paradigmatic Shastry-Sutherland model12-14 and displays exotic phenomena including magnetization plateaus15, low-lying bound-state excitations16, anomalous thermodynamics17 and discontinuous quantum phase transitions18,19. Here we control both the pressure and the magnetic field applied to SrCu2(BO3)2 to provide evidence of critical-point physics in a pure spin system. We use high-precision specific-heat measurements to demonstrate that, as in water, the pressure-temperature phase diagram has a first-order transition line that separates phases with different local magnetic energy densities, and that terminates at an Ising critical point. We provide a quantitative explanation of our data using recently developed finite-temperature tensor-network methods17,20-22. These results further our understanding of first-order quantum phase transitions in quantum magnetism, with potential applications in materials where anisotropic spin interactions produce the topological properties23,24 that are useful for spintronic applications.
RESUMEN
Skin wounds can lead to numerous complications with dangerous health consequences. In this work, magnetite nanoparticles were doped with different concentrations of antimicrobial silver (Ag) ions and incorporated into the electrospun nanofibrous ε-polycaprolactone (PCL) scaffolds. Nanoparticles and scaffolds with various Ag contents were characterized using a range of physicochemical techniques. Ag entered magnetite as cations and preferentially positioned at tetrahedral sites, introducing lattice distortions and topographic irregularities. Amorphization of the structure due to accommodation of Ag expanded the lattice in the bulk and contracted it on the surface, where broadened distribution of Fe-O coordinations was detected. Promoting spin canting and diminishing the double exchange interaction through altered distribution of ferric and ferrous ions, Ag softened the magnetism of magnetite. By making the nanoparticle structure more defective, Ag modified the interface with the polymer and promoted the protrusion of the nanoparticles from the surface of the polymeric nanofibers, thus increasing their roughness and hydrophilicity, with positive repercussions on cell adhesion and growth. Both the viability of human melanocytes and the antibacterial activity against E. coli and S. aureus increased with the concentration of Ag in the magnetite phase of the scaffolds. Skin wound healing rate in rats also increased in direct proportion with the concentration of Ag in the magnetite phase, and no abnormalities in the dermal and epidermal tissues were visible on day 10 in the treatment group. These results imply an excellent potential of these composite nanofibrous scaffolds for use as wound dressings and in other reconstructive skin therapies.
RESUMEN
AIMS: Patients with heart failure (HF) have high costs, morbidity, and mortality, but it is not known if appropriate pharmacotherapy (AP), defined as compliance with international evidence-based guidelines, is associated with improved costs and outcomes. The purpose of this study was to evaluate HF patients' health care utilization, cost and outcomes in Region Halland (RH), Sweden, and if AP was associated with lower costs. METHODS AND RESULTS: A total of 5987 residents of RH in 2016 carried HF diagnoses. Costs were assigned to all health care utilization (inpatient, outpatient, emergency department, primary health care, and medications) using a Patient Encounter Costing methodology. Care of HF patients cost 58.6 M, (9790/patient) representing 8.7% of RH's total visit expenses and 14.9% of inpatient care (IPC) expenses. Inpatient care represented 57.2% of this expenditure, totalling 33.5 M (5601/patient). Receiving AP was associated with significantly lower costs, by 1130 per patient (P < 0.001, 95% confidence interval 574-1687). Comorbidities such as renal failure, diabetes, chronic obstructive pulmonary disease, and cancer were significantly associated with higher costs. CONCLUSION: Heart failure patients are heavy users of health care, particularly IPC. Receiving AP is associated with lower costs even adjusting for comorbidities, although causality cannot be proven from an observational study. There may be an opportunity to decrease overall costs and improve outcomes by improving prescribing patterns and associated high-quality care.
Asunto(s)
Insuficiencia Cardíaca , Servicio de Urgencia en Hospital , Gastos en Salud , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/terapia , Hospitalización , Humanos , Suecia/epidemiologíaAsunto(s)
Mano , Hiperlipoproteinemia Tipo II/patología , Tendones , Xantomatosis/patología , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/etiología , Adulto , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Humanos , Hiperlipoproteinemia Tipo II/complicaciones , Hiperlipoproteinemia Tipo II/diagnóstico , Masculino , Xantomatosis/complicacionesRESUMEN
Due to the toxicity of lead(ii) to all living organisms as it destroys the central nervous system leading to circulatory system and brain disorders, the development of effective and selective lead(ii) ionophores for its detection is very important. In this work, 1,3-bis[2-(N-morpholino)acetamidophenoxy]propane (BMAPP), belonging to acyclic diamides, was applied as a highly selective lead(ii) ionophore in a carbon paste ion selective electrode for the accurate and precise determination of Pb(ii) ions even in the presence of other interfering ions. Factors affecting the electrode's response behavior were studied and optimized. Scanning electron microscopy (SEM), energy dispersive X-ray (EDX) and FT-IR spectroscopy were used for studying the morphology and response mechanism of the prepared sensor. The lipophilicity of the used ionophore, which contributes to the mechanical stability of the sensor, was studied using the contact angle measurement technique. The selectivity coefficients obtained by the separate solution method (SSM) and fixed interference method (FIM) confirmed the selectivity of the proposed sensor for Pb(ii) ions. The proposed sensor exhibited a Nernstian slope of 29.96 ± 0.34 mV per decade over a wide linear range of 5 × 10-8 to 1 × 10-1 mol L-1 and detection limit of 3 × 10-8 mol L-1 for 2 months with a fast response time (<10 s) and working pH range (2.5-5.5). To further ensure the practical applicability of the sensor, it was successfully applied for the lead(ii) ion determination in different water samples and the obtained data showed an agreement with those obtained by atomic absorption spectroscopy. In addition, it was successfully applied for the potentiometric titration of Pb(ii) against K2CrO4 and Na2SO4.
RESUMEN
Structural and molecular properties of HL, 4-amino-5-(2,2-dichloro-1-methylcyclopropyl)-4H-1,2,4-triazole-3-thiol toward the transition metal ions namely Fe(III), Co(II) and Ni(II) had been studied using elemental analyses, magnetic, electronic, FT- IR, 1H-NMR and Thermal analyses (TGA and DTA). The interpretation of thermal decomposition stages had been evaluated. The computations had been done by software of Gaussian 09W package. The geometries of triazole-thiole ligand and its metal chelates were fully optimized using density functional theory B3LYP method. (DFT)/GENECP level by implementing Def2TZVP basis set was used for Fe, Co and Ni-atoms; and basis set 6-311++G (d, p) was used for remainder atoms. There are no symmetry constrains had been applied during geometry optimization. The mixed basis set was selected due to its flexibility. HOMO and LUMO energy values for chelates, chemical hardness and electronegativity had been calculated. NBO calculations had been done at the same level using (NBO 3.1) program involved in the software of Gaussian 09W for measurement qualitatively the intra-molecular delocalization in systems under investigation. The first 15, 85, 65 and 65 low-lying excited states for ligand and Fe, Co and Ni chelates respectively had been calculated within the vertical linear-response. TD-DFT approximation at the same level of theory was used to calculate the electronic absorption spectra of the studied compounds. Their structures are confirmed by successful correlation between experimental and theoretical calculations. The ligand and its metal chelates had been examined against two bacteria such as Gram-positive (Staphylococcus aureus ATTC 12600), GraM-Negative (Escherichia coli ATTC 11775) and two fungus (Aspergillus flavus and Candida albicans) and molecular docking using Auto Dock tools were utilized.
Asunto(s)
Antibacterianos/farmacología , Antifúngicos/farmacología , Quelantes/farmacología , Complejos de Coordinación/farmacología , Compuestos de Sulfhidrilo/farmacología , Triazoles/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antifúngicos/síntesis química , Antifúngicos/química , Aspergillus/efectos de los fármacos , Candida albicans/efectos de los fármacos , Quelantes/síntesis química , Quelantes/química , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Teoría Funcional de la Densidad , Escherichia coli/efectos de los fármacos , Ligandos , Pruebas de Sensibilidad Microbiana , Teoría Cuántica , Programas Informáticos , Staphylococcus aureus/efectos de los fármacos , Compuestos de Sulfhidrilo/síntesis química , Compuestos de Sulfhidrilo/química , Temperatura , Triazoles/síntesis química , Triazoles/químicaRESUMEN
In this study, a novel bioflocculant QZ-7 was produced from Bacillus salmalaya 139SI for industrial wastewater treatment. Biochemical analysis, FTIR, scanning electron microscopy-energy dispersive X-ray spectroscopy, and thermogravimetric analysis were performed. A synthetic wastewater sample was used to validate the performance of the prepared OZ-7 for the adsorption efficiency of As, Zn2+ Pb2+, Cu2+, and Cd2+ under optimal experimental conditions such as initial metal concentrations, pH, contact time (h) and QZ-7 adsorbent dosage (mg mL-1). The maximum removal efficiency for Zn2+ (81.3%), As (78.6%), Pb2+ (77.9%), Cu2+ (76.1%), and Cd2+ (68.7%) was achieved using an optimal bioflocculant dosage of 60 mg L-1 at 2 h shaking time, 100 rpm and pH 7. Furthermore, the obtained optimum experimental conditions were validated using real industrial wastewater and the removal efficiencies of 89.8%, 77.4% and 58.4% were obtained for As, Zn2+ and Cu2+, respectively. The results revealed that the prepared bioflocculant QZ-7 has the capability to be used for the removal of heavy metals from industrial wastewater.
RESUMEN
The production, optimization, and characterization of the bioflocculant QZ-7 synthesized by a novel Bacillus salmalaya strain 139SI isolated from a private farm soil in Selangor, Malaysia, are reported. The flocculating activity of bioflocculant QZ-7 present in the selected strain was found to be 83.3%. The optimal culture for flocculant production was achieved after cultivation at 35.5 °C for 72 h at pH 7 ± 0.2, with an inoculum size of 5% (v/v) and sucrose and yeast extract as carbon and nitrogen sources. The maximum flocculating activity was found to be 92.6%. Chemical analysis revealed that the pure bioflocculant consisted of 79.08% carbohydrates and 15.4% proteins. The average molecular weight of the bioflocculant was calculated to be 5.13 × 105 Da. Infrared spectrometric analysis showed the presence of carboxyl (COO-), hydroxyl (-OH), and amino (-NH2) groups, polysaccharides and proteins. The bioflocculant QZ-7 exhibited a wide pH stability range from 4 to 7, with a flocculation activity of 85% at pH 7 ± 0.2. In addition, QZ-7 was thermally stable and retained more than 80% of its flocculating activity after being heated at 80 °C for 30 min. SEM analysis revealed that QZ-7 exhibited a clear crystalline brick-shaped structure. After treating wastewater, the bioflocculant QZ-7 showed significant flocculation performance with a COD removal efficiency of 93%, whereas a BOD removal efficiency of 92.4% was observed in the B. salmalaya strain 139SI. These values indicate the promising applications of the bioflocculant QZ-7 in wastewater treatment.
Asunto(s)
Bacillus/química , Glicoproteínas/biosíntesis , Aguas Residuales/química , Purificación del Agua/métodos , Bacillus/metabolismo , Carbono/química , Medios de Cultivo/química , Floculación , Cromatografía de Gases y Espectrometría de Masas , Glicoproteínas/química , Concentración de Iones de Hidrógeno , Peso Molecular , Nitrógeno/químicaRESUMEN
In the present work novel para chloro, para fluoro and para nitro maleanilic acid derivatives were prepared and investigated using FT-IR, thermal analyses (TA) measurements (TGA/DTG and DTA) in comparison with mass spectral (MS) fragmentation at 70 eV. The crystallographic structures of studied compounds were investigated by X-ray diffraction (XRD). The vibrational frequencies and the corresponding normal modes were evaluated at the optimized geometry. Vibrational modes were analyzed using GAUSSVIEW software. Experimental FT-IR and Raman spectra of the three newly prepared derivatives, namely, (E) - oxo -4- ((4- nitro phenyl) amino)-4- oxobut-2-enoic acid (p-NMA), (E) -4- ((4- chloro phenyl)amino)-4- oxobut -2- enoic acid (p-ClMA), (E) -4- ((4- fluoro phenyl) amino)- 4- oxobut -2- enoic acid (p-FMA) were compared with the theoretically calculated one. FT-IR and the observed vibrational frequencies were assigned; thermal analysis and mass spectrum measurements of the maleanilic acid derivatives were recorded and discussed. The computational calculations were carried out by DFT - B3LYP method with 6-311++G(d,p) basis sets and the corresponding results were tabulated. The alternations of structures of p-FMA, p-ClMA and p-NMA due to the subsequent substitutions were investigated. This correlation between experimental and theoretical calculations provided a good confirmation of the proposed structures of the newly prepared compounds. The derivatives were found to be highly effective against Hepatocellular carcinoma cells > Breast carcinoma cells > colon carcinoma cells. It was recognized, that cancer cells over expression promotes tumorigenic functions; can be suppressed by p-NMA > p-FMA > p-ClMA inhibitors.
RESUMEN
STUDY OBJECTIVE: The objective of this study was to assess short-term benefits and risks of utero-vaginal anastomosis done for cases of cryptomenorrhea due to cervical atresia with vaginal aplasia. DESIGN: Prospective study. SETTING: Surgical procedures were done between December 2013 and September 2015 at the department of Obstetrics and Gynecology, Cairo University Hospital. PARTICIPANTS: Five patients who had cryptomenorrhea due to cervical atresia associated with vaginal aplasia were included. INTERVENTIONS: Utero-vaginal anastomoses were performed in 2 stages; a stage of McIndoe vaginoplasty and a stage of excision of the atretic cervical tissue and anastomosing the uterus to the neovagina. Follow-up was done by gynecological and ultrasound examination in a duration ranged from 12 to 36 months. MAIN OUTCOME MEASURES: Occurrence of regular menstrual flow and relief of the severe cyclic pain. RESULTS: All patients had relief of the severe cyclic pain. Four patients had regular menstrual flow. One patient developed occlusion of the track after 1 year and needed dilatation once. Three patients developed low vaginal stenosis without occlusion of the track. One patient had rectal injury repaired without causing postoperative morbidity. CONCLUSION: Uterovaginal anastomosis is a promising conservative management option for cervical atresia with vaginal aplasia, which has benefits but is not free of risks. Long-term follow-up is still needed to judge its feasibility. We recommend performing McIndoe vaginoplasty as a starting stage before the anastomosis preferably in a separate setting.
Asunto(s)
Anastomosis Quirúrgica/métodos , Cuello del Útero/anomalías , Anomalías Congénitas/cirugía , Útero/cirugía , Vagina/anomalías , Adolescente , Adulto , Amenorrea , Anastomosis Quirúrgica/efectos adversos , Cuello del Útero/cirugía , Femenino , Estudios de Seguimiento , Hematómetra/etiología , Hematómetra/cirugía , Humanos , Menstruación , Estudios Prospectivos , Medición de Riesgo , Resultado del Tratamiento , Útero/anomalías , Vagina/cirugía , Adulto JovenRESUMEN
Oral cancer, a type of head and neck cancer, is ranked as one of the top most malignancies in India. Herein, we evaluated the anticancer efficacy of Abrus agglutinin (AGG), a plant lectin, in oral squamous cell carcinoma. AGG selectively inhibited cell growth, and caused cell cycle arrest and mitochondrial apoptosis through a reactive oxygen species (ROS)-mediated ATM-p73 dependent pathway in FaDu cells. AGG-induced ROS accumulation was identified as the major mechanism regulating apoptosis, DNA damage and DNA-damage response, which were significantly reversed by ROS scavenger N-acetylcysteine (NAC). Moreover, AGG was found to interact with mitochondrial manganese-dependent superoxide dismutase that might inhibit its activity and increase ROS in FaDu cells. In oral cancer p53 is mutated, thus we focused on p73; AGG resulted in p73 upregulation and knock down of p73 caused a decrease in AGG-induced apoptosis. Interestingly, AGG-dependent p73 expression was found to be regulated by ROS, which was reversed by NAC treatment. A reduction in the level of p73 in AGG-treated shATM cells was found to be associated with a decreased apoptosis. Moreover, administration of AGG (50 µg/kg body weight) significantly inhibited the growth of FaDu xenografts in athymic nude mice. In immunohistochemical analysis, the xenografts from AGG-treated mice displayed a decrease in PCNA expression and an increase in caspase-3 activation as compared to the controls. In conclusion, we established a connection among ROS, ATM and p73 in AGG-induced apoptosis, which might be useful in enhancing the therapeutic targeting of p53 deficient oral squamous cell carcinoma.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Carcinoma de Células Escamosas/tratamiento farmacológico , Daño del ADN/efectos de los fármacos , Neoplasias de la Boca/tratamiento farmacológico , Lectinas de Plantas/uso terapéutico , Proteína Tumoral p73/metabolismo , Abrus/química , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Ratones , Ratones Desnudos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/patología , Modelos Moleculares , Boca/efectos de los fármacos , Boca/metabolismo , Boca/patología , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Lectinas de Plantas/química , Lectinas de Plantas/farmacología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0163209.].
RESUMEN
BACKGROUND/OBJECTIVES: Elevated triglycerides predict insulin resistance and vascular disease in obesity, but how the inert triglyceride molecule is related to development of metabolic disease is unknown. To pursue novel potential mediators of triglyceride-associated metabolic disease, we used a forward genetics approach involving inbred mice and translated our findings to human subjects. SUBJECTS/METHODS: Hemopexin (HPX) was identified as a differentially expressed gene within a quantitative trait locus associated with serum triglycerides in an F16 advanced intercross between the LG/J and SM/J strains of mice. Hpx expression was evaluated in both the reproductive fat pads and livers of mice representing three strains, LG/J (n=25), SM/J (n=27) and C57Bl/6J (n=19), on high- and low-fat diets. The effect of altered Hpx expression on adipogenesis was studied in 3T3-L1 cells. Circulating HPX protein along with HPX expression were characterized in subcutaneous white adipose tissue samples obtained from a cohort of metabolically abnormal (n=18) and of metabolically normal (n=24) obese human subjects. We further examined the relationship between HPX and triglycerides in human atherosclerotic plaques (n=18). RESULTS: HPX expression in mouse adipose tissue, but not in liver, was regulated by dietary fat regardless of genetic background. HPX increased in concert with adipogenesis in 3T3-L1 cells, and disruption of its expression impaired adipocyte differentiation. RNAseq data from the adipose tissue of obese humans showed differential expression of HPX based on metabolic disease status (P<0.05), and circulating HPX levels were correlated with serum triglycerides in these subjects (r=0.33; P=0.03). HPX was also found in an unbiased proteomic screen of human atherosclerotic plaques and shown to display differential abundance based on the extent of disease and triglyceride content (P<0.05). CONCLUSIONS: Our findings suggest that HPX is associated with triglycerides and provide a framework for understanding mechanisms underlying lipid metabolism and metabolic disease.