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BACKGROUND: In kidney damage, molecular changes can be used as early damage kidney biomarkers, such as Kidney Injury Molecule-1 and Neutrophil gelatinase-associated lipocalin. These biomarkers are associated with toxic metal exposure or disturbed homeostasis of trace elements, which might lead to serious health hazards. This study aimed to evaluate the relationship between exposure to trace elements and early damage kidney biomarkers in a pediatric population. METHODS: In Tlaxcala, a cross-sectional study was conducted on 914 healthy individuals. The participants underwent a medical review and a socio-environmental questionnaire. Five early damage kidney biomarkers were determined in the urine with Luminex, and molybdenum, copper, selenium, nickel, and iodine were measured with ICP-Mass. RESULTS: The eGFR showed a median of 103.75 mL/min/1.73 m2. The median levels for molybdenum, copper, selenium, nickel, and iodine were 24.73 ng/mL, 73.35 ng/mL, 4.78 ng/mL, 83.68 ng/mL, and 361.83 ng/mL, respectively. Except for molybdenum and nickel, the other trace elements had significant associations with the eGFR and the early kidney damage biomarkers. Additionally, we report the association of different exposure scenarios with renal parameters. DISCUSSION: and Conclusions. Among the explored metals, exposure to Cu and iodine impairs renal function. In contrast, Se may manifest as a beneficial metal. Interactions of Mo-Se and Mo-Iodine seem to alter the expression of NGAL; Mo-Cu for CLU; Mo-Cu, Mo-Se, and Mo-iodine for Cys-C and a-1MG; and Mo-Cu and Mo-iodine for KIM-1; were noticed. Our study could suggest that trace element interactions were associated with early kidney damage biomarkers.
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Biomarcadores , Exposição Ambiental , Oligoelementos , Humanos , Biomarcadores/urina , Biomarcadores/metabolismo , Criança , Masculino , Feminino , Oligoelementos/análise , Oligoelementos/urina , Exposição Ambiental/efeitos adversos , Estudos Transversais , Adolescente , Lipocalina-2/urina , Taxa de Filtração Glomerular , Cobre/urina , Cobre/análise , Selênio/urina , Selênio/análise , Nefropatias/induzido quimicamente , Nefropatias/urina , Nefropatias/metabolismo , Rim/metabolismo , Pré-Escolar , Níquel/urinaRESUMO
This study aimed to identify the motivations of sports tourists to attend Soccer World Cups and to determine the motivational dimensions that predict their satisfaction. The research took place in Doha, the capital of Qatar, during the FIFA World Cup in 2022, where 503 valid questionnaires were collected. Exploratory factor analysis and linear regression with the Enter method were used for data analysis. The results show four motivational dimensions: Sports Passion, Escape & Relaxation, Patriotism & Attachment, and Recreation. Additionally, a positive and significant relationship was found between the Escape & Relaxation factor and overall satisfaction. In contrast, a negative correlation was identified between the Patriotism & Attachment dimension and satisfaction. These findings will contribute to the academic literature related to the Soccer World Cups as part of sports tourism and will also assist sporting event organizers in developing marketing and management plans to benefit this tourist demand.
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Osteosarcoma is a bone cancer primarily affecting teenagers. It has a poor prognosis and diminished quality of life after treatment due to chemotherapy side effects, surgical complications and post-surgical osteoporosis risks. The sulphated polysaccharide fucoidan, derived from brown algae, has been a subject of interest for its potential anti-cancer properties and its impact on bone regeneration. This study explores the influence of crude, low-molecular-weight (LMW, 10-50 kDa), medium-molecular-weight (MMW, 50-100 kDa) and high-molecular-weight (HMW, >100 kDa) fractions from Sargassum filipendula, harvested from the Colombian sea coast, as well as crude fucoidan from Fucus vesiculosus, on a specific human osteoprogenitor cell type, human embryonic-derived mesenchymal stem cells. Fourier transform infrared spectroscopy coupled with attenuated total reflection (FTIR-ATR) results showed the highest sulphation levels and lowest uronic acid content in crude extract from F. vesiculosus. There was a dose-dependent drop in focal adhesion formation, proliferation and osteogenic differentiation of cells for all fucoidan types, but the least toxicity was observed for LMW and MMW. Transmission electron microscopy (TEM), JC-1 (5,50,6,60-tetrachloro-1,10,3,30-tetraethylbenzimi-dazolylcarbocyanine iodide) staining and cytochrome c analyses confirmed mitochondrial damage, swollen ER and upregulated autophagy due to fucoidans, with the highest severity in the case of F. vesiculosus fucoidan. Stress-induced apoptosis-like cell death by F. vesiculosus fucoidan and stress-induced necrosis-like cell death by S. filipendula fucoidans were also confirmed. LMW and MMW doses of <200 ng/mL were the least toxic and showed potential osteoinductivity. This research underscores the multifaceted impact of fucoidans on osteoprogenitor cells and highlights the delicate balance between potential therapeutic benefits and the challenges involved in using fucoidans for post-surgery treatments in patients with osteosarcoma.
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Filipendula , Fucus , Osteossarcoma , Sargassum , Humanos , Adolescente , Sargassum/química , Fucus/química , Osteogênese , Qualidade de Vida , Polissacarídeos/farmacologia , Polissacarídeos/química , Osteossarcoma/tratamento farmacológicoRESUMO
The land transport sector, impacting fossil fuel consumption, has been selected as one of the sectors to apply decarbonization strategies. Energy systems modelling is an applied tool to evaluate scenarios and strategies that can be implemented in the transport sector to achieve energy transitions. These energy modelling tools need a dataset that allows the simulation of alternative scenarios of the systems. For this purpose, a collection and processing of technical-economic data is needed to ensure a quality input for simulation tools. This article presents a set of open data to create a model of the energy system of the Dominican Republic to assess alternative scenarios and develop strategies to achieve the energy transition in the land transport sector. This exercise is performed to support the energy planning policies of the country. Although the dataset is presented for the conditions of the Dominican Republic, the insight regarding data gathering and processing can be applied to other island countries. The data obtained are an open-access database of energy regulators, generation agents, and representatives of the generation, transmission, and distribution sector, as well as websites, databases of international organizations, scientific journals, and standards. Therefore, the data presented can be updated as the technical-economic information becomes public.
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Chemotherapy is a widely used strategy to treat cancer, a disease that causes millions of deaths each year. However, its efficacy is reduced by the overexpression of ABC transporters, which are proteins that expel the drugs used in chemotherapy and involved in the multidrug resistance (MDR). Glycolipids have been identified as potential inhibitors of ABC transporters. Algae of the genus Sargassum contain high levels of glycolipids, making them a promising therapeutic alternative against the MDR phenotype. Sargassum filipendula glycolipids were obtained by exhaustive maceration with chloroform/methanol, purified by column and thin layer chromatography, and then characterized by FTIR, NMR, and LC-MS. Cell viability by PI labeling and inhibition of ABC transporters were analyzed by flow cytometry. Assessment of resistance reversal was determined by MTT assay. Ten sulfoquinovosylglycerol-type compounds were found, and six of them are reported for the first time. In particular, moiety 4 (GL-4) showed strong and moderate inhibitory activity against ABCC1 and ABCB1 transporters respectively. Treatment of GL-4 in combination with the antineoplastic drug vincristine sensitized Lucena-1â cell model to drug and reversed the MDR phenotype. This is the first report of glycolipids isolated from S. filipendula capable of inhibiting ABC transporters and thus overcoming acquired drug resistance.
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Antineoplásicos , Filipendula , Neoplasias , Sargassum , Humanos , Transportadores de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/farmacologia , Sargassum/metabolismo , Resistencia a Medicamentos Antineoplásicos , Resistência a Múltiplos Medicamentos , Antineoplásicos/farmacologia , Antineoplásicos/química , Neoplasias/metabolismo , Linhagem Celular TumoralRESUMO
BACKGROUND: Sarcopenia is a condition associated with aging and multiple medical conditions such as CKD and hypovitaminosis D. METHODS: An observational cross-sectional study was carried out, based on patients registered in a database of specialized nephrology consultation in the city of Manizales, Colombia. 101 patients over 18 years of age who had stage 3 or 4 CKD were included. RESULTS: The frequency of sarcopenia was 10.9%. No relationship was found between sarcopenia alone and serum vitamin D levels. However, when sarcopenia was categorized as severe there was a direct relationship with hypovitaminosis D. There was also a direct relationship between dynapenia and hypovitaminosis D. In addition, patients who had serum vitamin D levels above 40 ng/ml had better muscle performance, and, consequently, probably a lower risk of frailty. CONCLUSION: When patients, within their treatment, received vitamin D supplementation, no effect on muscle performance was observed.
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Insuficiência Renal Crônica , Sarcopenia , Deficiência de Vitamina D , Humanos , Adolescente , Adulto , Colômbia/epidemiologia , Sarcopenia/epidemiologia , Estudos Transversais , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Vitamina D , Insuficiência Renal Crônica/complicaçõesRESUMO
AI-based chatbots are an emerging technology disrupting the tourism industry. Although chatbots have received increasing attention, there is little evidence of their impact on tourists' decisions to visit a destination. This study evaluates the key attributes of chatbots and their effects on user satisfaction and visit intention. We use structural equation modeling with covariance procedures to test the proposed model and its hypotheses. The results showed that informativeness, empathy, and interactivity are critical attributes for satisfaction, which drive tourists' intention to visit a destination.
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Empatia , Intenção , Indústrias , Análise de Classes Latentes , Inteligência ArtificialRESUMO
The antioxidant and the potential inhibitory capacity of matrix metalloproteinases of the phlorotannin-type polyphenolic and fucoidan-type polysaccharides extracts obtained from the macroalga S. filipendula were evaluated. Through chromatographic and spectroscopic techniques, the corresponding chemical structure of compounds present in the extracts was determined. Antioxidant capacity was evaluated using the methyl linoleate model for the inhibition of lipid peroxidation, and the free radical scavenging capacity was assessed using DPPH, ABTS, â¢OH, O2â¢- methods. The matrix metalloproteinase inhibition potential was measured by collagenase and elastase inhibition tests, using epigallocatechin gallate as a positive control. The extracts exhibited a high scavenging capacity of radical species evaluated and inhibition of diene conjugate formation and thiobarbituric acid reactive substances. The results showed that the crude extracts presented dose-dependent collagenase and elastase inhibition, with IC50 values between 0.04 and 1.61 mg/mL. The structure of the residues of the polysaccharide was identified mainly as (1â3)-sulfated (1â3) α-l-fucopyranose at carbon 4 and residues of ß-d-glucopyranose, α-d-Mannopyranose, and ß-d-Galactopyranose, while in the polyphenol extract the presence of phloroglucinol was identified and the presence of eckol, bifuhalol, and trifuhalol was suggested. Our results allow us to infer that S. filipendula is a potential source of bioactive ingredients with antioxidant and anti-aging activity.
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Overexposure to solar radiation has become an increasingly worrying problem due to the damage to the skin caused by ultraviolet radiation (UVR). In previous studies, the potential of an extract enriched with glycosylated flavonoids from the endemic Colombian high-mountain plant Baccharis antioquensis as a photoprotector and antioxidant was demonstrated. Therefore, in this work we sought to develop a dermocosmetic formulation with broad-spectrum photoprotection from the hydrolysates and purified polyphenols obtained from this species. Hence, the extraction of its polyphenols with different solvents was evaluated, followed by hydrolysis and purification, in addition to the characterization of its main compounds by HPLC-DAD and HPLC-MS, and evaluation of its photoprotective capacity through the measurement of the Sun Protection Factor (SPF), UVA Protection Factor (UVAPF), other Biological Effective Protection Factors (BEPFs), and its safety through the cytotoxicity. In the dry methanolic extract (DME) and purified methanolic extract (PME), flavonoids such as quercetin and kaempferol were found, which demonstrated antiradical capacity, as well as UVA-UVB photoprotection and prevention of harmful biological effects, such as elastosis, photoaging, immunosuppression, DNA damage, among others, which demonstrates the potential of the ingredients in this type of extract to be applied in photoprotection dermocosmetics.
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Wild mushrooms have gained great importance for being a source of biologically active compounds. In this work, we evaluate the anticancer and antioxidant activity of a water-soluble crude polysaccharide extract isolated from the fruiting bodies of the Ganoderma aff. australe (GACP). This mushroom was collected in San Mateo (Boyacá, Colombia) and identified based on macroscopic and microscopic characterization. GACP was characterized by UV-Vis spectroscopy, Fourier-transform infrared spectroscopy, high-performance liquid chromatography-diode array detector, and nuclear magnetic resonance. The antiradical and antioxidant activity were evaluated by different methods and its anticancer activity was verified in the osteosarcoma MG-63 human cell line. Chemical and spectroscopic analysis indicated that GACP consisted of ß-D-Glcp-(1â, â3)-ß-D-Glcp-(1â and α-D-Glcp-(1â residues. The results of the biological activity showed that GACP exhibited high antioxidant activity in the different methods and models studied. Moreover, the results showed that GACP impaired cell viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay) and cell proliferation (clonogenic assay) in a dose-response manner on MG-63 cells. The findings of this work promote the use of mushroom-derived compounds as anticancer and antioxidant agents for potential use in the pharmaceutical and food industries.
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Agaricales , Ganoderma , Humanos , Antioxidantes/química , Água , Ganoderma/química , Polissacarídeos/química , Agaricales/químicaRESUMO
Purpose: Determination and development of an effective set of models leveraging Artificial Intelligence techniques to generate a system able to support clinical practitioners working with COVID-19 patients. It involves a pipeline including classification, lung and lesion segmentation, as well as lesion quantification of axial lung CT studies. Approach: A deep neural network architecture based on DenseNet is introduced for the classification of weakly-labeled, variable-sized (and possibly sparse) axial lung CT scans. The models are trained and tested on aggregated, publicly available data sets with over 10 categories. To further assess the models, a data set was collected from multiple medical institutions in Colombia, which includes healthy, COVID-19 and patients with other diseases. It is composed of 1,322 CT studies from a diverse set of CT machines and institutions that make over 550,000 slices. Each CT study was labeled based on a clinical test, and no per-slice annotation took place. This enabled a classification into Normal vs. Abnormal patients, and for those that were considered abnormal, an extra classification step into Abnormal (other diseases) vs. COVID-19. Additionally, the pipeline features a methodology to segment and quantify lesions of COVID-19 patients on the complete CT study, enabling easier localization and progress tracking. Moreover, multiple ablation studies were performed to appropriately assess the elements composing the classification pipeline. Results: The best performing lung CT study classification models achieved 0.83 accuracy, 0.79 sensitivity, 0.87 specificity, 0.82 F1 score and 0.85 precision for the Normal vs. Abnormal task. For the Abnormal vs COVID-19 task, the model obtained 0.86 accuracy, 0.81 sensitivity, 0.91 specificity, 0.84 F1 score and 0.88 precision. The ablation studies showed that using the complete CT study in the pipeline resulted in greater classification performance, restating that relevant COVID-19 patterns cannot be ignored towards the top and bottom of the lung volume. Discussion: The lung CT classification architecture introduced has shown that it can handle weakly-labeled, variable-sized and possibly sparse axial lung studies, reducing the need for expert annotations at a per-slice level. Conclusions: This work presents a working methodology that can guide the development of decision support systems for clinical reasoning in future interventionist or prospective studies.
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The fruiting bodies of edible mushrooms represent an important source of biologically active polysaccharides. In this study, Lentinula edodes crude polysaccharides (LECP) were extracted in hot water, and their antioxidant and antiradical activities were investigated. The antioxidant activity of LECP was investigated against reactive species such as 1,1'-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid, hydroxyl and superoxide anion radicals, reducing power with EC50 values of 0.51, 0.52, 2.19, 3.59 and 1.73 mg/mL, respectively. Likewise, LECP inhibited the lipid peroxidation induced in methyl linoleate through the formation of conjugated diene hydroperoxide and malondialdehyde. The main sugar composition of LECP includes mannose, galactose, glucose, fucose and glucuronic acid. Characterization by Fourier transform infrared spectroscopy and nuclear magnetic resonance determined that LECP was made up of α and ß glycosidic bonds with a backbone of α-D-Glc, â6)-ß-D-Glcp-(1â, â6)-α-D-Galp-(1â and ß-D-Manp-(1â residues. The results showed that LECP can scavenge all reactive species tested in a concentration-dependent manner and with a protective effect in the initial and final stages of lipid peroxidation. The natural antioxidant activity of the LECP that was investigated strengthens the high medicinal and nutritional value of this mushroom.
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OBJECTIVE: To harmonize participants' information from five epidemiological studies. MATERIALS AND METHODS: The Mexican Consortium of Epidemiological Studies for the Prevention, Diagnosis, and Treatment of Chronic Kidney Disease (RenMex, by its Spanish acronym) was established in 2018. RenMex is a consortium of five studies: The Mexican Teachers Cohort Study; the Mexico City Diabetes Study; the Health Workers Cohort Study; the Comitán Study; and the Salt Consumption in Mexico Study, which assessed baseline serum creatinine, albumin, and C-reactive protein, all performed with standardized techniques. RESULTS: RenMex includes 3 133 participants, with a mean age of 44.8 years, 68.8% women, 10.8% with a previous medical diagnosis of type 2 diabetes, and 24.1% living with obesity. CONCLUSIONS: In the future, RenMex will work on more detailed analyses with each cohort allowed to opt in or out for each topic according to their individual data.
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Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Adulto , Proteína C-Reativa , Estudos de Coortes , Creatinina , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Feminino , Humanos , Masculino , México/epidemiologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapiaRESUMO
Expectations about a destination influence the tourist experience during the travel process stages. In the post-COVID-19 normalcy, people are adjusting their priorities and social values. Therefore, it becomes crucial to identify tourists' expectations before traveling. The objectives of this research were: (a) identify the preferences of tourists; (b) establish the attitudes of tourists; and (c) determine the expectations of tourists for post-COVID-19 destination selection. The study analyzed a sample of 491 people during pandemic lockdowns in Guayaquil, Ecuador. Statistical techniques such as exploratory and confirmatory factor analysis were used in data analysis. The results show that after the pandemic, tourists prefer urban tourism, followed by cultural tourism and traveling with relatives. It also shows a more responsible and supportive attitude when traveling. Likewise, the results support the dimensional structure that explains a set of post-pandemic tourist expectations. Five factors were identified: Smart Care, pricing strategy, safety, comfort, and social distancing. Finally, the theoretical and managerial implications of the results that will guide for tourism destination managers were discussed.
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COVID-19 , Atitude , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Equador/epidemiologia , Humanos , Motivação , ViagemRESUMO
The photoprotective and antioxidant activities of extracts of six species of plants collected in a high mountain ecosystem at 3150 m.a.s.l. were evaluated. In vitro photoprotection according to UVA-UVB absorption spectrum, Sun Protection Factor (SPF), UVA Protection Factor (UVAPF), (critical wavelength) λc and UVA/UVB Ratio were assessed. Also, the antioxidant activity was determined using the DPPH radical assay and the inhibition of lipid peroxidation in methyl linoleate (MeLo). Total anthocyanins content (TAC) and total polyphenolic content (TPC) were evaluated. Among the extracts evaluated, the extract of B. antioquensis, an endemic plant of Colombia, showed a significant photoprotection against UVA-UVB range, with SPF values of 15 ± 2 and UVAPF of 7 ± 1, λc : 378, UVA/UVB Ratio: 0.78. Furthermore, this extract presented an excellent antioxidant activity, with EC50 of 0.17 ± 0.04 g of dry extract/mmol DPPH, a value of TPC of 464 ± 9 mg gallic acid equivalents (GAE)/g dry extract and significant inhibition of MeLo peroxidation. The results suggest that the extract of B. antioquensis has the best quality to be a source of new UV filters, with a broad spectrum of protection and antioxidant properties.
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Antioxidantes , Protetores Solares , Antocianinas , Antioxidantes/química , Antioxidantes/farmacologia , Ecossistema , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas , Protetores Solares/química , Protetores Solares/farmacologia , Raios UltravioletaRESUMO
Abstract The histological structure and biochemistry of the skin is affected by solar radiation having adverse effects ranging from sunburns, premature aging that includes wrinkles, spots, dryness, and loss of collagen to cancer development. The skin has defense mechanisms to prevent damage caused by radiation, but when radiation exposure is excessive these mechanisms are not strong enough to protect the skin. The use of sunscreen is the most common practice of photo- protection. The active ingredients of these cosmetic protective formulations are generally from synthetic origin and have presented several drawbacks at the level of photo-stability, systemic absorption and can generate contact and photo-contact dermatitis. This review illustrates skin solar radiation problems, common sunscreen ingredients limitation and mentions how algae can be an alternative according to studies that have evaluated the photo-protective potential of extracts and compounds isolated by different techniques.
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Pele/patologia , Protetores Solares/administração & dosagem , Radiação Solar , Alga Marinha/classificação , Dermatopatias , Colágeno/administração & dosagem , Exposição à Radiação/prevenção & controle , Absorção Fisiológica/efeitos dos fármacosRESUMO
The aim of this study was to develop a new hybrid biomaterial that could photo-stabilize and improve the photoprotective capacity of a Baccharis antioquensis extract. Different combinations of lignin/gelatin/natural extract were applied to prepare hybrid biomaterial nanoparticles (NPs), which were then incorporated into an emulsion. The in vitro photoprotection and photostability were evaluated. The methanolic extract showed high phenolic content (646.4 ± 9.5 mg GAE/g dry extract) and a DPPH radical assay revealed that the antiradical capacity of the extract (0.13 to 0.05 g extract/mmol DPPH) was even better than that of BHT. The particle size of the hybrid biomaterial ranged from 100 to 255 nm; a polydispersity index (PdI) between 0.416 and 0.788 is suitable for topical use in dermocosmetic products. The loading capacity of the extract ranged from 27.0 to 44.5%, and the nanoparticles (NPs) showed electrostatic stability in accordance with the zeta potential value. We found that the formulation based on lignin: extract (1:1 ratio) and gelatin: lignin: extract (0.5:0.5:1 ratio) demonstrated photoprotection qualities with a sun protection factor (SPF) ranging from 9.4 to 22.6. In addition, all the hybrid NP-formulations were time-stable with %SPFeff and %UVAPFeff greater than 80% after exposure to 2 h of radiation. These results suggest that the hybrid biopolymer-natural extract improved the photoprotection and photostability properties, as well as the antiradical capacity, of the B. antioquensis extract, and may be useful for trapping high polyphenol content from natural extracts, with potential application in cosmeceutical formulations.
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Most of the plant species found in the high mountain ecosystems of the tropics is unique and exceptional, because they have developed complex adaptations to survive in extreme environmental conditions, such as high levels of UVR and low temperatures of these ecological environments. In an exploratory study carried out on some plants of this ecosystem, we found that one of the most promising species was the Pentacalia pulchella (Kunth) Cuatrec. (Asteraceae) an endemic plant of Colombia, which grows between 2500 and 3500 m.a.s.l. Therefore, the objective of this work was to evaluate the photoprotective, antioxidant, and chemical composition of extracts from the leaves of P. pulchella. Extracts showed good absorption coefficients in UVA-UVB, high content of total phenols, with antioxidant activity comparable to that obtained with butylhydroxytoluene (BHT). Finally, the formulation labeled "7" with 10% extract presented adequate sensory characteristics for topical use, good in vitro photoprotection values in the UVA-UVB range (SPF (Sun Protection Factor): 7.3 ± 0.9, UVAPF (Ultraviolet A Protection Factor): 5.3 ± 0.6, λc 376), and antioxidant activity. Results obtained allow us to suggest that the extract of P. pulchella has a high potential as a source of new natural solar filters.
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Antioxidantes , Asteraceae , Antioxidantes/farmacologia , Ecossistema , Extratos Vegetais/farmacologia , Pele , Protetores Solares/farmacologia , Raios UltravioletaRESUMO
Fucoidan is a brown algae-derived polysaccharide having several biomedical applications. This study simultaneously compares the anti-cancer activities of crude fucoidans from Fucus vesiculosus and Sargassum filipendula, and effects of low (LMW, 10-50 kDa), medium (MMW, 50-100 kDa) and high (HMW, >100 kDa) molecular weight fractions of S. filipendula fucoidan against osteosarcoma cells. Glucose, fucose and acid levels were lower and sulphation was higher in F. vesiculosus crude fucoidan compared to S. filipendula crude fucoidan. MMW had the highest levels of sugars, acids and sulphation among molecular weight fractions. There was a dose-dependent drop in focal adhesion formation and proliferation of cells for all fucoidan-types, but F. vesiculosus fucoidan and HMW had the strongest effects. G1-phase arrest was induced by F. vesiculosus fucoidan, MMW and HMW, however F. vesiculosus fucoidan treatment also caused accumulation in the sub-G1-phase. Mitochondrial damage occurred for all fucoidan-types, however F. vesiculosus fucoidan led to mitochondrial fragmentation. Annexin V/PI, TUNEL and cytochrome c staining confirmed stress-induced apoptosis-like cell death for F. vesiculosus fucoidan and features of stress-induced necrosis-like cell death for S. filipendula fucoidans. There was also variation in penetrability of different fucoidans inside the cell. These differences in anti-cancer activity of fucoidans are applicable for osteosarcoma treatment.
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Linhagem Celular Tumoral/efeitos dos fármacos , Polissacarídeos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Fucus/química , Humanos , Mitocôndrias/efeitos dos fármacos , Peso Molecular , Osteossarcoma , Phaeophyceae/química , Sargassum/químicaRESUMO
The formation of the KRas4B-PDEδ complex activates different signaling pathways required for the development and maintenance of cancer. Previous experimental and theoretical studies have allowed researchers to design an inhibitor of the KRas4B-PDEδ complex, "Deltarasin." This inhibitor binds to the prenyl-binding pocket of PDEδ and subsequently inhibits the proliferation of human pancreatic ductal adenocarcinoma cells that depend on oncogenic KRas4B. Nevertheless, structural and energetic information about the inhibitory effects of Deltarasin on the KRas4B-PDEδ complex are not available. In this study, we explore the properties of Deltarasin in inhibiting the formation of wild-type and mutant KRas4B-PDEδ complexes present in different cell lines expressing mutant RAS genes (G12D, G12C, G12V, G13D, Q61L, and Q61R) using 1.7 µs molecular dynamics (MD) simulations in combination with the MMGBSA approach. Our results revealed the energetic and structural mechanisms that suggest a higher affinity of Deltarasin for PDEδ than the farnesylated HVR. Moreover, Deltarasin exerts another dissociative effect by binding to the protein-protein dimeric interface of wild-type KRas4B-PDEδ, whereas associative and dissociative effects were observed for mutant KRas4B-PDEδ, providing a mechanistic explanation for the inhibitory effects of Deltarasin on different cancer cell lines.