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Lipid oxidation is the major cause of the deterioration of fat-containing foods, especially those containing polyunsaturated fatty acids (PUFAs). Antioxidant additives of synthetic origin are added to matrices rich in PUFAs, such as sunflower oil (SO). However, there is controversy regarding their safety, and their low solubility in both water and fat has led to the search for new covalent modifications through lipophilicity. This work presents the synthesis of O-alkyl acid derivatives from ferulic and syringic acids and the study of their antioxidant capacity and effect on the thermoxidative degradation of SO. Antioxidant activities were evaluated by employing ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays in a concentration range of 10-100 µg mL-1. The IC50 values for DPPH scavenging activity ranged from 15.61-90.43 µg mL-1. The results of the FRAP assay for both O-alkyl ferulic (3a-f) and syringic (5a-f) series revealed a "cut-off" effect on antioxidant activity in carbon five (C5). Thermoxidation study of additives 3b-c and 5b-c showed a decrease in the slope of extinction coefficients K 232 and K 270 in comparison with SOcontrol. Furthermore, 3c presented higher antioxidant activity than 3b and 1, with a power to decrease the thiobarbituric acid reactive species (TBARS) 6 times higher than SOcontrol at 220 °C. Additives 5b-c exerted a protective effect on the thermoxidation of SO. The results suggest that increasing lipophilic and thermal properties of antioxidants through O-alkyl acid derivatization is an effective strategy for accessing lipophilic antioxidant additives with potential use in food matrices.
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A novel Coumarin-based 1,2-pyrazole, HCPyTSC is synthesised and characterized. The chemosensor has been shown to have efficient colourimetric and fluorescence sensing capabilities for the quick and selective detection of fluoride and copper ions. At 376 and 430 nm, the HCPyTSC exhibits selective sensing for Cu2+ and F- ions. By examining the natural bond orbital (NBO) analysis and the potential energy curve (PES) of the ground state for the function of the C-H bond, it has been determined from the theoretical study at hand that the deprotonation was taken from the 'CH' proton of the pyrazole ring. For F- and Cu2+, the HCPyTSC detection limits were 4.62 nM and 15.36 nM, respectively. Similarly, the binding constants (Kb) for F- and Cu2+ ions in acetonitrile medium were found to be 2.06 × 105 M-1 and 1.88 × 105 M-1. Chemosensor HCPyTSC with and without F- and Cu2+ ions have an emission and absorption response that can imitate a variety of logic gates, including the AND, XOR, and OR gates. Additionally, a paper-based sensor strip with the HCPyTSC was created for use in practical, flexible F- sensing applications. The paper-based sensor was more effective in detecting F- than other anions. The effectiveness of HCPyTSC for the selective detection of F- in living cells as well as its cell permeability were examined using live-cell imaging in T24 cells.
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The ability to differentiate into cells of different lineages, such as bone cells, is the principal value of adult mesenchymal stem cells (MSCs), which can be used with the final aim of regenerating damaged tissue. Due to its potential use and importance in regenerative medicine and tissue engineering, several questions have been raised regarding the molecular mechanisms of MSC differentiation. As one of the crucial mediators in organism development, the transforming growth factor-beta (TGF-ß) superfamily directs MSCs' commitment to selecting differentiation pathways. This review aims to give an overview of the current knowledge on the mechanisms of the TGF-ß superfamily in MSCs bone differentiation, with additional insight into the mutual regulation of microRNAs and TGF-ß in osteogenesis.
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Células Madre Mesenquimatosas , MicroARNs , Osteogénesis/genética , MicroARNs/genética , MicroARNs/metabolismo , Diferenciación Celular/genética , Factor de Crecimiento Transformador beta/metabolismo , Factores de Crecimiento Transformadores/metabolismoRESUMEN
A novel fluorescence chemosensor BDP (2-(1-(benzothiazol-2-yl)-5-(4-(diphenylamino)phenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenol) has been synthesized and its sensing behavior has been screened towards various cations by absorption, emission and mass spectroscopic techniques. The probe BDP detects Cu2+ ions preferentially over other metal ions, and the resulting BDP-Cu2+ ensemble acts as a secondary sensor for cyanide anion detection over other anions. The fluorescence intensity of the probe BDP is quenched when it comes into contact with Cu2+ ions, but it is increased reversibly when it comes into contact with cyanide anion, according to spectroscopic measurements. Along with this, optical studies indicate that the sensor BDP has capability to sense Cu2+ and CN- ions selectively over other examined competitive ions with the LOD of 2.57×10-8 M and 2.98×10-8 M respectively. The detection limit of Cu2+ ions is lower than the WHO recommended Cu2+ ions concentration (31.5 µM) in drinking water. On the basis of "on-off-on" fluorescence change of the probe BDP upon interaction with Cu2+ and CN- ions, a possible mechanism for this selective sensing behavior was presented and IMPLICATION logic gate was successfully designed. Furthermore, cell imaging investigations were used to investigate the probe BDP's biological applicability.
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Half-sandwich Ru(II) complexes containing nitro-substituted furoylthiourea ligands, bearing the general formula [(η6-p-cymene)RuCl2(L)] (1-6) and [(η6-p-cymene)RuCl(L)(PPh3)]+ (7--12), have been synthesized and characterized. In contrast to the spectroscopic data which revealed monodentate coordination of the ligands to the Ru(II) ion via a "S" atom, single crystal X-ray structures revealed an unusual bidentate N, S coordination with the metal center forming a four-membered ring. Interaction studies by absorption, emission, and viscosity measurements revealed intercalation of the Ru(II) complexes with calf thymus (CT) DNA. The complexes showed good interactions with bovine serum albumin (BSA) as well. Further, their cytotoxicity was explored exclusively against breast cancer cells, namely, MCF-7, T47-D, and MDA-MB-231, wherein all of the complexes were found to display more pronounced activity than their ligand counterparts. Complexes 7-12 bearing triphenylphosphine displayed significant cytotoxicity, among which complex 12 showed IC50 values of 0.6 ± 0.9, 0.1 ± 0.8, and 0.1 ± 0.2 µM against MCF-7, T47-D, and MDA-MB-231 cell lines, respectively. The most active complexes were tested for their mode of cell death through staining assays, which confirmed apoptosis. The upregulation of apoptotic inducing and downregulation of apoptotic suppressing proteins as inferred from the western blot analysis also corroborated the apoptotic mode of cell death. The active complexes effectively generated reactive oxygen species (ROS) in MDA-MB-231 cells as analyzed from the 2',7'-dichlorofluorescein diacetate (DCFH-DA) staining. Finally, in vivo studies of the highly active complexes (6 and 12) were performed on the mice model. Histological analyses revealed that treatment with these complexes at high doses of up to 8 mg/kg did not induce any visible damage to the tested organs.
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Antineoplásicos , Complejos de Coordinación , Neoplasias , Rutenio , Animales , Ratones , Ligandos , Complejos de Coordinación/química , Cimenos/farmacología , Cimenos/química , Apoptosis , Antineoplásicos/química , Rutenio/farmacología , Rutenio/química , Línea Celular TumoralRESUMEN
Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020 and ranking as the second-leading cause of death in economically developed countries [...].
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Hemostasis preserves blood fluidity and prevents its loss after vessel injury. The maintenance of blood fluidity requires a delicate balance between pro-coagulant and fibrinolytic status. Endothelial cells (ECs) in the inner face of blood vessels maintain hemostasis through balancing anti-thrombotic and pro-fibrinolytic activities. Dyslipidemias are linked to hemostatic alterations. Thus, it is necessary a better understanding of the underlying mechanisms linking hemostasis with dyslipidemia. Statins are drugs that decrease cholesterol levels in the blood and are the gold standard for treating hyperlipidemias. Statins can be classified into natural and synthetic molecules, approved for the treatment of hypercholesterolemia. The classical mechanism of action of statins is by competitive inhibition of a key enzyme in the synthesis pathway of cholesterol, the HMG-CoA reductase. Statins are frequently administrated by oral ingestion and its interaction with other drugs and food supplements is associated with altered bioavailability. In this review we deeply discuss the actions of statins beyond the control of dyslipidemias, focusing on the actions in thrombotic modulation, vascular and cardiovascular-related diseases, metabolic diseases including metabolic syndrome, diabetes, hyperlipidemia, and hypertension, and chronic diseases such as cancer, chronic obstructive pulmonary disease, and chronic kidney disease. Furthermore, we were prompted to delved deeper in the molecular mechanisms by means statins regulate coagulation acting on liver, platelets, and endothelium. Clinical evidence show that statins are effective regulators of dyslipidemia with a high impact in hemostasis regulation and its deleterious consequences. However, studies are required to elucidate its underlying molecular mechanism and improving their therapeutical actions.
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Enfermedades Cardiovasculares , Dislipidemias , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Hiperlipidemias , Trombosis , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Células Endoteliales , Hemostasis , Trombosis/prevención & control , Enfermedades Cardiovasculares/tratamiento farmacológico , Colesterol , Dislipidemias/tratamiento farmacológicoRESUMEN
Catecholamine stimulation over adrenergic receptors results in a state of hypercoagulability. Chronic stress involves the release and increase in circulation of catecholamines and other stress related hormones. Numerous observational studies in human have related stressful scenarios to several coagulation variables, but controlled stimulation with agonists or antagonists to adrenergic receptors are scarce. This systematic review is aimed at presenting an updated appraisal of the effect of adrenergic receptor modulation on variables related to human hemostasis by systematically reviewing the effect of adrenergic receptor-targeting drugs on scale variables related to hemostasis. By searching 3 databases for articles published between January 1st 2011 and February 16th, 2022 reporting effects on coagulation parameters from stimulation with α- or ß-adrenergic receptor targeting drugs in humans regardless of baseline condition, excluding records different from original research and those not addressing the main aim of this systematic review. Risk of bias assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2). Tables describing a pro-thrombotic anti-fibrinolytic state induced after ß-adrenergic receptor agonist stimulation and the opposite after α1-, ß-adrenergic receptor antagonist stimulation were synthesized from 4 eligible records by comparing hemostasis-related variables to their baseline. Notwithstanding this low number of records, experimental interventions included were sound and mostly unbiased, results were coherent, and outcomes were biologically plausible. In summary, this systematic review provides a critical systematic assessment and an updated elaboration, and its shortcomings highlight the need for further investigation in the field of hematology.
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Adrenérgicos , Hemostasis , Receptores Adrenérgicos , Catecolaminas , Receptores Adrenérgicos/metabolismo , Adrenérgicos/uso terapéutico , Hemostasis/efectos de los fármacos , Humanos , Estrés Fisiológico , Coagulación SanguíneaRESUMEN
Dexmedetomidine is an adrenergic receptor agonist that has been regarded as neuroprotective in several studies without an objective measure to it. Thus, the aim of this meta-analysis was to analyze and quantify the current evidence for the neuroprotective effects of dexmedetomidine in animals. The search was performed by querying the National Library of Medicine. Studies were included based on their language, significancy of their results, and complete availability of data on animal characteristics and interventions. Risk of bias was assessed using SYRCLE's risk of bias tool and certainty was assessed using the ARRIVE Guidelines 2.0. Synthesis was performed by calculating pooled standardized mean difference and presented in forest plots and tables. The number of eligible records included per outcome is the following: 22 for IL-1ß, 13 for IL-6, 19 for apoptosis, 7 for oxidative stress, 7 for Escape Latency, and 4 for Platform Crossings. At the cellular level, dexmedetomidine was found protective against production of IL-1ß (standardized mean difference (SMD) = - 4.3 [- 4.8; - 3.7]) and IL-6 (SMD = - 5.6 [- 6.7; - 4.6]), apoptosis (measured through TUNEL, SMD = - 6.0 [- 6.8; - 4.6]), and oxidative stress (measured as MDA production, SMD = - 2.0 [- 2.4; - 1.4]) exclusively in the central nervous system. At the organism level, dexmedetomidine improved behavioral outcomes measuring escape latency (SMD = - 2.4 [- 3.3; - 1.6]) and number of platform crossings (SMD = 9.1 [- 6.8; - 11.5]). No eligible study had high risk of bias and certainty was satisfactory for reproducibility in all cases. This meta-analysis highlights the complexity of adrenergic stimulation and sheds light into the mechanisms potentiated by dexmedetomidine, which could be exploited for improving current neuroprotective formulations.
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Dexmedetomidina , Fármacos Neuroprotectores , Estados Unidos , Interleucina-6 , Reproducibilidad de los ResultadosRESUMEN
A simple D - A (donor - acceptor) type receptor ((2E, 2'E)-3, 3'-(10-octyl-10H-phenothiazine-3,7-diyl)bis(2-(benzo[d]thiazol-2-yl)acrylonitrile)) (PBTA) containing nitrile-vinyl linkage was designed and completely characterized. The receptor PBTA detects CN- ions based on "turn-off" effect with admirable spectral properties. It also owns some of the merits like "naked-eye" color change, ultrafast response (90 s), lowest detection limit (1.25 × 10-10 M) as well as quantitation limit (4.17 × 10-10 M) with the pH range 4-11 which is more suitable pH to make use of the receptor PBTA in physiological medium. The instant detecting ability of the receptor over CN- ions was proved using paper test strip and cotton balls. Further, the utilization of the receptor PBTA was also extended to track CN- ions in realistic samples (water and food samples) and in HeLa cells bioimaging.
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Cianuros , Nitrilos , Humanos , Células HeLa , Agua/química , Colorantes Fluorescentes/químicaRESUMEN
Sepsis syndrome develops through enhanced secretion of pro-inflammatory cytokines and the generation of reactive oxygen species (ROS). Sepsis syndrome is characterized by vascular hyperpermeability, hypotension, multiple organ dysfunction syndrome (MODS), and increased mortality, among others. Endotoxemia-derived sepsis is an important cause of sepsis syndrome. During endotoxemia, circulating endotoxin interacts with endothelial cells (ECs), inducing detrimental effects on endothelium function. The endotoxin induces the conversion of ECs into fibroblasts, which are characterized by a massive change in the endothelial gene-expression pattern. This downregulates the endothelial markers and upregulates fibrotic proteins, mesenchymal transcription factors, and extracellular matrix proteins, producing endothelial fibrosis. Sepsis progression is modulated by the consumption of specific nutrients, including ω-3 fatty acids, ascorbic acid, and polyphenolic antioxidant flavonoids. However, the underlying mechanism is poorly described. The notion that gene expression is modulated during inflammatory conditions by nutrient consumption has been reported. However, it is not known whether nutrient consumption modulates the fibrotic endothelial gene-expression pattern during sepsis as a mechanism to decrease vascular hyperpermeability, hypotension, MODS, and mortality. Therefore, the aim of this study was to investigate the impact of the consumption of dietary ω-3 fatty acids, ascorbic acid, and polyphenolic antioxidant flavonoid supplements on the modulation of fibrotic endothelial gene-expression patterns during sepsis and to determine the effects on sepsis outcomes. Our results indicate that the consumption of supplements based on ω-3 fatty acids and polyphenolic antioxidant flavonoids was effective for improving endotoxemia outcomes through prophylactic ingestion and therapeutic usage. Thus, our findings indicated that specific nutrient consumption improves sepsis outcomes and should be considered in treatment.
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We set out to design and synthesize bipodal ligands with the phenyl group as the spacer and varied the substitution on the spacer between ortho (L1), meta (L2), and para (L3). The respective ligands and complexes containing either p-cymene (PL1-PL3) or benzene (BL1-BL3) as the arene unit were synthesized and characterized successfully. The influence of the ligands due to substitution change on their coordination behavior was quite minimal; however, the differences were seen in the anticancer activity of the complexes. DFT studies revealed the structural variations between the three different substitutions, which was further confirmed by single-crystal X-ray diffraction studies. The anticancer activity of the complexes could be correlated with their rate of hydrolysis and their lipophilicity index as determined by UV-visible spectroscopy. The cell death mechanism of the active complexes was deduced to be apoptotic via staining assays, flow cytometry, and Western blot analysis.
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Antineoplásicos , Complejos de Coordinación , Rutenio , Línea Celular Tumoral , Antineoplásicos/química , Complejos de Coordinación/química , Ligandos , Cimenos , Rutenio/químicaRESUMEN
A colorimetric probe TQA ((E)-4-(((8-(sec-butoxy)-2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-9-yl)methylene)amino)benzylacrylate) possessing greater potent towards the sensing of cysteine was successfully synthesized and characterized. The aqueous soluble probe TQA detects Cys based on "ON-OFF" effect with excellent absorbance and emission properties. The probe TQA detects Cys up to its ultra-low level concentration of 1.5 nM and also quantifies the Cys up to 5.05 nM with the quicker response time of 140 s (2.3 min). In addition, the color change produced by the probe TQA on integrated with Cys was also identified easily via paper strip, cotton wool buds and RGB color picker app in smart mobiles. Further, the admirable selectivity and sensitivity of the probe TQA towards Cys extends its utility towards food samples and imaging of live HeLa cells.
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Cisteína , Agua , Humanos , Células HeLa , Acrilatos , Colorantes FluorescentesRESUMEN
BACKGROUND: Oxidative stress derived from severe systemic inflammation promotes conversion from high-density lipoprotein HDL to oxidized HDL (oxHDL), which interacts with vascular endothelial cells (ECs). OxHDL acquires procoagulant features playing a role in modulating coagulation, which has been linked with organ failure in ICU patients. However, whether oxHDL elicits a ECs-mediated procoagulant phenotype generating organ failure and death, and the underlying molecular mechanism is not known. Therefore, we studied whether oxHDL-treated rats and high-oxHDL ICU patients exhibit a procoagulant phenotype and its association with kidney injury and mortality and the endothelial underlying molecular mechanism. METHODS: Human ECs, oxHDL-treated rats and ICU patients were subjected to several cellular and molecular studies, coagulation analyses, kidney injury assessment and mortality determination. RESULTS: OxHDL-treated ECs showed a procoagulant protein expression reprograming characterized by increased E-/P-selectin and vWF mRNA expression through specific signaling pathways. OxHDL-treated rats exhibited a procoagulant phenotype and modified E-/P-selectin, vWF, TF and t-PA mRNA expression correlating with plasma TF, t-PA and D-dimer. Also, showed increased death events and the relative risk of death, and increased creatinine, urea, BUN/creatinine ratio, KIM-1, NGAL, ß2M, and decreased eGFR, all concordant with kidney injury, correlated with plasma TF, t-PA and D-dimer. ICU patients showed correlation between plasma oxHDL and increased creatinine, cystatin, BUN, BUN/creatinine ratio, KIM-1, NGAL, ß2M, and decreased GFR. Notably, ICU high-oxHDL patients showed decreased survival. Interestingly, altered coagulation factors TF, t-PA and D-dimer correlated with both increased oxHDL levels and kidney injury markers, indicating a connection between these factors. CONCLUSION: Increased circulating oxHDL generates an endothelial-dependent procoagulant phenotype that associates with acute kidney injury and increased risk of death.
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Lesión Renal Aguda , Lipoproteínas HDL , Humanos , Ratas , Animales , Lipoproteínas HDL/metabolismo , Selectina-P/metabolismo , Células Endoteliales/metabolismo , Creatinina , Lipocalina 2 , Factor de von Willebrand/metabolismo , Fenotipo , ARN MensajeroRESUMEN
INTRODUCCIÓN: La cuantificación de SARS-CoV-2 en aguas residuales es una herramienta que permite determinar la tendencia de la circulación viral en un área geográfica determinada. OBJETIVO: Cuantificar el virus SARS-CoV-2 en 15 plantas de tratamiento de aguas residuales en diferentes ciudades de Chile para establecer una comparación con las variables de: i) casos activos por cada 100.000 habs.; ii) positividad diaria (casos nuevos); y iii) fases del plan de confinamiento. METODOLOGÍA: SARS-CoV-2 se concentró a partir de muestras de aguas residuales. Para obtener el número de genomas del virus por litro se realizó una cuantificación absoluta utilizando qRT-PCR. RESULTADOS: Entre enero y junio de 2021 se procesaron 253 muestras, siendo todas positivas para la presencia del virus. Asimismo, se logró determinar que la tasa de casos activos por cada 100.000 habs. es la variable que mejor se ajusta a las tendencias obtenidas con la cuantificación de la carga viral en las aguas residuales. CONCLUSIONES: La cuantificación de SARS-CoV-2 en las aguas residuales de manera permanente es una herramienta eficiente para determinar la tendencia del virus en un área geográfica determinada y, en conjunto con una vigilancia genómica, puede constituirse en una vigilancia centinela ideal generando alertas sobre futuros brotes.
BACKGROUND: The quantification of SARS-CoV-2 in wastewater is a tool that allows determining the trend of viral circulation in a particular geographical area. AIM: To quantify the SARS-CoV-2 virus in 15 wastewater treatment plants in different Chilean cities to establish a comparison with the variables of: i) Active cases per 100,000 inhabitants; ii) daily positivity (novel cases); and iii) phases of the lockdown strategy. METHODS: SARS-CoV-2 was concentrated from wastewater samples. To obtain the number of virus genomes per liter, absolute quantification was performed using qRT-PCR. RESULTS: Between January and June 2021, 253 samples were processed, all of which were positive for the presence of the virus. Likewise, it will be determined that the rate of active cases per 100,000 inhabitants is the variable that best fits the trends obtained with the quantification of the viral load in wastewater. CONCLUSIONS: The quantification of SARS-CoV-2 in wastewater as a continuous strategy is an efficient tool to determine the trend of the viral circulation in a delimited geographical area and, combined with genomic surveillance, it can constitute an ideal sentinel surveillance alert on future outbreaks.
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Humanos , Aguas Residuales/virología , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/genética , COVID-19/epidemiología , ARN Viral/genética , Chile/epidemiología , Carga Viral , Genómica , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Monitoreo Epidemiológico Basado en Aguas ResidualesRESUMEN
Background: There is abundant ethnopharmacological evidence the uses of regarding Solanum species as antitumor and anticancer agents. Glycoalkaloids are among the molecules with antiproliferative activity reported in these species. Purpose: To evaluate the anticancer effect of the Solanum glycoalkaloid tomatine in hepatocellular carcinoma (HCC) in vitro (HepG2 cells) and in vivo models. Methods: The resazurin reduction assay was performed to detect the effect of tomatine on cell viability in human HepG2 cell lines. Programmed cell death was investigated by means of cellular apoptosis assays using Annexin V. The expression of cancer related proteins was detected by Western blotting (WB). Reactive oxygen species (ROS) and calcium were determined by 2,7-dichlorodihydrofluorescein diacetate and Fluo-4, respectively. Intrahepatic HepG2 xenograft mouse model was used to elucidate the effect of tomatine on tumor growth in vivo. Results and Discussion: Tomatine reduced HepG2 cell viability and induced the early apoptosis phase of cell death, consistently with caspase-3, -7, Bcl-2 family, and P53 proteins activation. Furthermore, tomatine increased intracellular ROS and cytosolic Ca+2 levels. Moreover, the NSG mouse xenograft model showed that treating mice with tomatine inhibited HepG2 tumor growth. Conclusion: Tomatine inhibits in vitro and in vivo HCC tumorigenesis in part via modulation of p53, Ca+2, and ROS signalling. Thus, the results suggest the potential cancer therapeutic use of tomatine in HCC patients.
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A pyrene-based fluorescent chemosensor APSB [N-(pyrene-1-ylmethylene) anthracen-2-amine] was designed and developed by a simple condensation reaction between pyrene carboxaldehyde and 2-aminoanthracene. The APSB fluorescent sensor selectively binds Fe3+ in the presence of other metal ions. Apart from this, APSB shows high selectivity and sensitivity toward Fe3+ ion detection. The detection limit for APSB was 1.95 nM, and the binding constant (K b) was obtained as 8.20 × 105 M-1 in DMSO/water (95/5, v/v) medium. The fluorescence quantum yields for APSB and APSB-Fe3+ were calculated as 0.035 and 0.573, respectively. The function of this fluorescent sensor APSB can be explained through the photo-induced electron transfer mechanism which was further proved by density functional theory studies. Finally, a live-cell image study of APSB in HeLa cells was also carried out to investigate the cell permeability of APSB and its efficiency for selective detection of Fe3+ in living cells.