RESUMEN
4D Flow Magnetic Resonance Imaging (4D Flow MRI) is a non-invasive measurement technique capable of quantifying blood flow across the cardiovascular system. While practical use is limited by spatial resolution and image noise, incorporation of trained super-resolution (SR) networks has potential to enhance image quality post-scan. However, these efforts have predominantly been restricted to narrowly defined cardiovascular domains, with limited exploration of how SR performance extends across the cardiovascular system; a task aggravated by contrasting hemodynamic conditions apparent across the cardiovasculature. The aim of our study was therefore to explore the generalizability of SR 4D Flow MRI using a combination of existing super-resolution base models, novel heterogeneous training sets, and dedicated ensemble learning techniques; the latter-most being effectively used for improved domain adaption in other domains or modalities, however, with no previous exploration in the setting of 4D Flow MRI. With synthetic training data generated across three disparate domains (cardiac, aortic, cerebrovascular), varying convolutional base and ensemble learners were evaluated as a function of domain and architecture, quantifying performance on both in-silico and acquired in-vivo data from the same three domains. Results show that both bagging and stacking ensembling enhance SR performance across domains, accurately predicting high-resolution velocities from low-resolution input data in-silico. Likewise, optimized networks successfully recover native resolution velocities from downsampled in-vivo data, as well as show qualitative potential in generating denoised SR-images from clinicallevel input data. In conclusion, our work presents a viable approach for generalized SR 4D Flow MRI, with the novel use of ensemble learning in the setting of advanced fullfield flow imaging extending utility across various clinical areas of interest.
RESUMEN
Hepatocellular carcinoma (HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Recently, the most unique technique used is liquid biopsies, which carry many markers; the most prominent is circulating tumor DNA (ctDNA). Varied methods are used to investigate ctDNA, including various forms of polymerase chain reaction (PCR) [emulsion PCR (ePCR), digital PCR (dPCR), and bead, emulsion, amplification, magnetic (BEAMing) PCR]. Hence ctDNA is being recognized as a potential biomarker that permits early cancer detection, treatment monitoring, and predictive data on tumor burden are subjective to therapy or surgery. Numerous ctDNA biomarkers have been investigated based on their alterations such as 1) single nucleotide variations (either insertion or deletion of a nucleotide) markers including TP53, KRAS, and CCND1; 2) copy number variations which include markers such as CDK6, EFGR, MYC and BRAF; 3) DNA methylation (RASSF1A, SEPT9, KMT2C and CCNA2); 4) homozygous mutation includes ctDNA markers as CDKN2A, AXIN1; and 5) gain or loss of function of the genes, particularly for HCC. Various researchers have conducted many studies and gotten fruitful results. Still, there are some drawbacks to ctDNA namely low quantity, fragment heterogeneity, less stability, limited mutant copies and standards, and differential sensitivity. However, plenty of investigations demonstrate ctDNA's significance as a polyvalent biomarker for cancer and can be viewed as a future diagnostic, prognostic and therapeutic agent. This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that facilitate its early identification.
RESUMEN
4D Flow Magnetic Resonance Imaging (4D Flow MRI) is a non-invasive measurement technique capable of quantifying blood flow across the cardiovascular system. While practical use is limited by spatial resolution and image noise, incorporation of trained super-resolution (SR) networks has potential to enhance image quality post-scan. However, these efforts have predominantly been restricted to narrowly defined cardiovascular domains, with limited exploration of how SR performance extends across the cardiovascular system; a task aggravated by contrasting hemodynamic conditions apparent across the cardiovasculature. The aim of our study was to explore the generalizability of SR 4D Flow MRI using a combination of heterogeneous training sets and dedicated ensemble learning. With synthetic training data generated across three disparate domains (cardiac, aortic, cerebrovascular), varying convolutional base and ensemble learners were evaluated as a function of domain and architecture, quantifying performance on both in-silico and acquired in-vivo data from the same three domains. Results show that both bagging and stacking ensembling enhance SR performance across domains, accurately predicting high-resolution velocities from low-resolution input data in-silico. Likewise, optimized networks successfully recover native resolution velocities from downsampled in-vivo data, as well as show qualitative potential in generating denoised SR-images from clinicallevel input data. In conclusion, our work presents a viable approach for generalized SR 4D Flow MRI, with ensemble learning extending utility across various clinical areas of interest.
RESUMEN
Using 3D CNNs on high-resolution medical volumes is very computationally demanding, especially for large datasets like UK Biobank, which aims to scan 100,000 subjects. Here, we demonstrate that using 2D CNNs on a few 2D projections (representing mean and standard deviation across axial, sagittal and coronal slices) of 3D volumes leads to reasonable test accuracy (mean absolute error of about 3.5 years) when predicting age from brain volumes. Using our approach, one training epoch with 20,324 subjects takes 20-50 s using a single GPU, which is two orders of magnitude faster than a small 3D CNN. This speedup is explained by the fact that 3D brain volumes contain a lot of redundant information, which can be efficiently compressed using 2D projections. These results are important for researchers who do not have access to expensive GPU hardware for 3D CNNs.
RESUMEN
Cancer has remained one of the leading causes of death worldwide, with a lack of effective treatment. The intrinsic shortcomings of conventional therapeutics regarding tumor specificity and non-specific toxicity prompt us to look for alternative therapeutics to mitigate these limitations. In this regard, we developed multifunctional bimetallic (FeCo) bi-MIL-88B-FC MOFs modified with folic acid-conjugated chitosan (FC) as drug delivery systems (DDS) for targeted delivery of 5-Fluorouracil (5-FU). The bi-MIL-88B nanocarriers were characterized through various techniques, including powder X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray, thermogravimetric analysis, and Fourier transform infrared spectroscopy. Interestingly, 5-FU@bi-MIL-88B-FC showed slower release of 5-FU due to a gated effect phenomenon endowed by FC surface coating compared to un-modified 5-FU@bi-MIL-88B. The pH-responsive drug release was observed, with 58% of the loaded 5-FU released in cancer cells mimicking pH (5.2) compared to only 24.9% released under physiological pH (5.4). The in vitro cytotoxicity and cellular internalization experiments revealed the superiority of 5-FU@bi-MIL-88B-FC as a highly potent targeted DDS against folate receptor (FR) positive SW480 cancer cells. Moreover, due to the presence of Fe and Co in the structure, bi-MIL-88B exhibited peroxidase-like activity for chemodynamic therapy. Based on the results, 5-FU@bi-MIL-88B-FC could serve as promising candidate for smart DDS by sustained drug release and selective targeting.
RESUMEN
Heliminthosporium oryzae is a necrotrophic fungal pathogen that effect rice crops grown on millions of hectares. We evaluated nine newly establishing rice lines and one local variety for resistance against H. oryzae. Significant (P ≤ 0.05) differences in response to pathogen attack were recorded in all rice lines. Maximum disease resistance was recorded in Kharamana under pathogen attack as compared to uninfected plants. A comparison of decline in shoot length revealed that Kharamana and Sakh experienced minimum lost (9.21%, 17.23%) in shoot length respectively against control while Binicol exhibited highest reduction (35.04%) in shoot length due to H. oryzae attack. Post-infection observations of shoot fresh weight revealed 63% decline in Binicol and declared it as the most susceptible rice line. Sakh, Kharamana and Gervex exhibited minimum fresh weight decrease (19.86%, 19.24% and 17.64% respectively) as compared to other lines under pathogen attack. Maximum chlorophyll-a contents were recorded in Kharamana under control and post pathogen attackconditions. Following the inoculation of H. oryzae, SOD was increased up to 35% and 23% in Kharamana and Sakh. However, minimum POD activity was recorded in Gervex followed by Swarnalata, Kaosen and C-13 in non-inoculated and pathogen-inoculated plants. Significant decrease in ascorbic acid contents (73.7% and 70.8%) was observed in Gervex and Binicol that later contributed in their susceptibility to H. oryzae attack. Pathogen attack caused Significant (P ≤ 0.05) changes in secondary metabolites in all rice lines but minimum total flavonoids, anthocyanin and lignin were observed in Binicol in uninfected plants and attested its susceptibility to pathogen. In post-pathogen attack conditions, Kharamana showed best resistance against pathogen by exhibiting a significantly high and maximum value of morpho-physiological, and biochemical attributes. Our findings suggest that tested resistant lines can be further explored for multiple traits including molecular regulation of defense responses to breed immunity in rice varieties.
Asunto(s)
Magnaporthe , Oryza , Oryza/microbiología , Enfermedades de las Plantas/microbiología , Resistencia a la Enfermedad , Plantas Modificadas GenéticamenteRESUMEN
Interaction of different pollutants can aggravate hazards to biotic components in agroecosystems. Microplastics (MPs) are especially needed to be focused on because of their increasing use in life around the globe. We investigated the interactive impacts of polystyrene microplastics (PS-MP) and lead (Pb) on mung bean (Vigna radiata L.). Toxicity of MPs and Pb directly impeded V. radiata attributes. In combination i.e., M2P2 (40 µM Pb + 4.0 mg L-1 MPs) predominantly reduced the shoot root fresh and dry weights. \ Pb and PS-MP impaired the Rubisco activity and chlorophyll contents. The dose dependent relationship (M2P2) discomposed indole 3-acetic acid by 59.02%. Individual treatments P2 (40 µM Pb) and M2 (4.0 mg L-1 MPs) respectively instigated a decline (44.07% and 27.12%) in IBA, while ABA was elevated. M2 significantly enhanced the contents of Alanine (Ala), Arginine (Arg), Proline (Pro), and glycine (Gly) by 64.11%, 63%, and 54% compared to control. Lysine (Lys) and Valine (Val) presented a converse relationship with other amino acids. Except for control, a gradual decline in yield parameters were observed in individual and combined applications of PS-MP. Proximate composition of carbohydrates, lipids and proteins also reflected a clear decrease in these compounds after combined application of Pb and MPs. Although, individual doses caused a decline in these compounds but effect of combined doses Pb and PS-MP was highly significant. Our results demonstrated the toxicity effect of Pb and MP in V. radiata attributes that is mainly linked with cumulative physiological and metabolic perturbations. These collective negative impacts of different doses of MPs and Pb on V. radiata would certainly pose serious implications for humans.
Asunto(s)
Fabaceae , Vigna , Contaminantes Químicos del Agua , Humanos , Poliestirenos/metabolismo , Microplásticos/metabolismo , Plásticos/metabolismo , Plomo/metabolismo , Fitoquímicos/metabolismo , Contaminantes Químicos del Agua/metabolismoRESUMEN
Along with the increasing incidence of cancer and drawbacks of traditional drug delivery systems (DDSs), developing novel nanocarriers for sustained targeted-drug release has become urgent. In this regard, metal-organic frameworks (MOFs) have emerged as potential candidates due to their structural flexibility, defined porosity, lower toxicity, and biodegradability. Herein, a FeMn-based ferromagnetic MOF was synthesized from a preassembled Fe2Mn(µ3-O) cluster. The introduction of the Mn provided the ferromagnetic character to FeMn-MIL-88B. 5-Fluoruracil (5-FU) was encapsulated as a model drug in the MOFs, and its pH and H2S dual-stimuli responsive controlled release was realized. FeMn-MIL-88B presented a higher 5-FU loading capacity of 43.8 wt % and rapid drug release behavior in a tumor microenvironment (TME) simulated medium. The carriers can rapidly release loaded drug of 70% and 26% in PBS solution (pH = 5.4) and NaHS solution (500 µM) within 24 h. The application of mathematical release models indicated 5-FU release from carriers can be precisely fitted to the first-order, second-order, and Higuchi models of release. Moreover, the cytotoxicity profile of the carrier against human embryonic kidney cells (HEK293T) suggests no adverse effects up to 100 µg/mL. The lesser toxic effect on cell viability can be attributed to the low toxicity values [LD50 (Fe) = 30 g·kg-1, (Mn) = 1.5 g·kg-1, and (terephthalic acid) = 5 g·kg-1] of the MOFs structural components. Together with dual-stimuli responsiveness, ferromagnetic nature, and low toxicity, FeMn-MIL-88B MOFs can emerge as promising carriers for drug delivery applications.
RESUMEN
Malignant pleural mesothelioma (MPM) is a fatal disease of respiratory system. Despite the availability of invasive biomarkers with promising results, there are still significant diagnostic and therapeutic challenges in the treatment of MPM. One of three main mesothelioma cell types, epithelioid mesothelioma makes up approximately 70% of all mesothelioma cases. Different observational findings are under process, but the molecular heterogeneity and pathogenesis of epithelioid malignant pleural mesothelioma (eMPM) are still not well understood. Through molecular analysis, expression profiling data were used to determine the possibility and optimal number of eMPM molecular subtypes. Next, clinicopathological characteristics and different molecular pathways of each subtype were analyzed to prospect the clinical applications and advanced mechanisms of eMPM. In this study, we identified two distinct epithelioid malignant pleural mesothelioma subtypes with distinct gene expression patterns. Subtype I eMPMs were involved in steroid hormone biosynthesis, porphyrin and chlorophyll metabolism, and drug metabolism, while subtype II eMPMs were involved in rational metabolism, tyrosine metabolism, and chemical carcinogenesis pathways. Additionally, we identified potential subtype-specific therapeutic targets, including CCNE1, EPHA3, RNF43, ROS1, and RSPO2 for subtype I and CDKN2A and RET for subtype II. Considering the need for potent diagnostic and therapeutic biomarkers for eMPM, we are anticipating that our findings will help both in exploring underlying mechanisms in the development of eMPM and in designing targeted therapy for eMPM.
Asunto(s)
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Porfirinas , Clorofila , Hormonas , Humanos , Neoplasias Pulmonares/patología , Mesotelioma/diagnóstico , Mesotelioma/genética , Neoplasias Pleurales/genética , Neoplasias Pleurales/patología , Proteínas Proto-Oncogénicas , Esteroides , TirosinaRESUMEN
Recent epidemiological data report that worldwide more than 53 million people have been infected by SARS-CoV-2, resulting in 1.3 million deaths. The disease has been spreading very rapidly and few months after the identification of the first infected, shortage of hospital resources quickly became a problem. In this work we investigate whether artificial intelligence working with chest X-ray (CXR) scans and clinical data can be used as a possible tool for the early identification of patients at risk of severe outcome, like intensive care or death. Indeed, further to induce lower radiation dose than computed tomography (CT), CXR is a simpler and faster radiological technique, being also more widespread. In this respect, we present three approaches that use features extracted from CXR images, either handcrafted or automatically learnt by convolutional neuronal networks, which are then integrated with the clinical data. As a further contribution, this work introduces a repository that collects data from 820 patients enrolled in six Italian hospitals in spring 2020 during the first COVID-19 emergency. The dataset includes CXR images, several clinical attributes and clinical outcomes. Exhaustive evaluation shows promising performance both in 10-fold and leave-one-centre-out cross-validation, suggesting that clinical data and images have the potential to provide useful information for the management of patients and hospital resources.
Asunto(s)
COVID-19 , Inteligencia Artificial , Humanos , Italia , SARS-CoV-2 , Rayos XRESUMEN
Pheochromocytoma (PCC) is a rare neuroendocrine tumor of the adrenal gland with a high rate of mortality if diagnosed at a late stage. Common symptoms of pheochromocytoma include headache, anxiety, palpitation, and diaphoresis. Different treatments are under observation for PCC but there is still no effective treatment option. Recently, the gene expression profiling of various tumors has provided new subtype-specific options for targeted therapies. In this study, using data sets from TCGA and the GSE19422 cohorts, we identified two distinct PCC subtypes with distinct gene expression patterns. Genes enriched in Subtype I PCCs were involved in the dopaminergic synapse, nicotine addiction, and long-term depression pathways, while genes enriched in subtype II PCCs were involved in protein digestion and absorption, vascular smooth muscle contraction, and ECM receptor interaction pathways. We further identified subtype specific genes such as ALK, IGF1R, RET, and RSPO2 for subtype I and EGFR, ESR1, and SMO for subtype II, the overexpression of which led to cell invasion and tumorigenesis. These genes identified in the present research may serve as potential subtype-specific therapeutic targets to understand the underlying mechanisms of tumorigenesis. Our findings may further guide towards the development of targeted therapies and potential molecular biomarkers against PCC.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/genética , Biomarcadores de Tumor/genética , Expresión Génica , Feocromocitoma/genética , Neoplasias de las Glándulas Suprarrenales/metabolismo , Bases de Datos Genéticas , Perfilación de la Expresión Génica , Humanos , Mutación , Feocromocitoma/metabolismo , Pronóstico , Proteínas Proto-Oncogénicas c-ret/genéticaRESUMEN
PURPOSE: We investigate, by an extensive quality evaluation approach, performances and potential side effects introduced in Computed Tomography (CT) images by Deep Learning (DL) processing. METHOD: We selected two relevant processing steps, denoise and segmentation, implemented by two Convolutional Neural Networks (CNNs) models based on autoencoder architecture (encoder-decoder and UNet) and trained for the two tasks. In order to limit the number of uncontrolled variables, we designed a phantom containing cylindrical inserts of different sizes, filled with iodinated contrast media. A large CT image dataset was collected at different acquisition settings and two reconstruction algorithms. We characterized the CNNs behavior using metrics from the signal detection theory, radiological and conventional image quality parameters, and finally unconventional radiomic features analysis. RESULTS: The UNet, due to the deeper architecture complexity, outperformed the shallower encoder-decoder in terms of conventional quality parameters and preserved spatial resolution. We also studied how the CNNs modify the noise texture by using radiomic analysis, identifying sensitive and insensitive features to the denoise processing. CONCLUSIONS: The proposed evaluation approach proved effective to accurately analyze and quantify the differences in CNNs behavior, in particular with regard to the alterations introduced in the processed images. Our results suggest that even a deeper and more complex network, which achieves good performances, is not necessarily a better network because it can modify texture features in an unwanted way.
Asunto(s)
Aprendizaje Profundo , Procesamiento de Imagen Asistido por Computador , Redes Neurales de la Computación , Fantasmas de Imagen , Tomografía Computarizada por Rayos XRESUMEN
Merkel cell carcinoma (MCC) is a rare primary cutaneous neoplasm of neuroendocrine carcinoma of the skin. About 80% of the MCC occurs due to Merkel cell polyomavirus (MCPyV) and 20% of the tumors usually occur due to severe UV exposure which is a more aggressive type of MCC. It tends to have an increased incidence rate among elderly and immunosuppressed individuals. On therapeutic level, sub-classification of MCC through molecular subtyping has emerged as a promising technique for MCC prognosis. In current study, two consistent distinct molecular subtypes of MCCs were identified using gene expression profiling data. Subtypes I MCCs were associated with spliceosome, DNA replication and cellular pathways. On the other hand, genes overexpressed in subtype II were found active in TNF signalling pathway and MAPK signalling pathway. We proposed different therapeutic targets based on subtype specificity, such as PTCH1, CDKN2A, AURKA in case of subtype I and MCL1, FGFR2 for subtype II. Such findings may provide fruitful knowledge to understand the intrinsic subtypes of MCCs and the pathways involved in distinct subtype oncogenesis, and will further advance the knowledge in developing a specific therapeutic strategy for these MCC subtypes.
RESUMEN
In the published original version, the complete list of authors was omitted. The complete list of contributing authors is updated with this Correction.
RESUMEN
Schiff base ligands are biologically active compounds in having antimicrobial, antiviral and antitumor activities etc. In this study, we have synthesized a Schiff base ligand namely 4-hydroxy-3-(2-hydroxy-3-methoxybenzylideneamino) benzoic acid, by reacting 3-amino-4-hydroxybenzoic acid and 2-hydroxy-3-methoxy benzaldehyde in the presence of acetic acid and refluxing it. The resulting base ligand was characterized on HPLC and used for radiolabelling with technetium-99m. The ligand 4-hydroxy-3-(2-hydroxy-3-methoxybenzylideneamino) benzoic acid was labelled with 99mTc at pH 7, while reacting 230 µg of ligand with 15 mCi of 99mTcO-4 for 10 min at room temperature. The resulting 99mTc-ligand complex was characterized by paper chromatography, TLC, HPLC and electrophoresis technique. The stability of the complex was determined at room temperature and in human serum. The biodistribution of the complex was studied in mice and scintigraphy was performed in rabbit. The 99mTc-ligand complex showed high radiolabelling yield (up to 99 ± 1%) and high stability at room temperature and in human serum. The newly prepared complex exhibited no net charge. Our newly developed 99mTc-ligand complex demonstrated high accumulation in liver and spleen of mice as well as in rabbit. Based on these findings, we have suggested that this novel radioligand i.e., 99mTc- 4-hydroxy-3-(2-hydroxy-3-methoxybenzylideneamino) benzoic acid complex could be used for liver and spleen imaging.
Asunto(s)
Benzoatos/síntesis química , Eliminación Hepatobiliar/efectos de los fármacos , Animales , Benzoatos/uso terapéutico , Ácido Benzoico , Ligandos , Masculino , Ratones , Compuestos de Organotecnecio/química , Conejos , Radioisótopos/química , Cintigrafía , Radiofármacos/análisis , Radiofármacos/química , Tecnecio/química , Distribución TisularRESUMEN
Development of curcumin-loaded mixed polymeric micelles based on chitosan, alginate, maltodextrin, pluronic F127, pluronic P123, and tween 80, by thin-film hydration method has been investigated in Bisphenol A induced diabetics rats. Curcumin (C21H20O6) extracted from rhizomes of the "Curcuma longa" has attracted considerable attention of pharmaceutical researchers due to its low cost, excellent pharmacological activities and lesser side effects. Despite its diverse pharmacological properties, the therapeutic application of curcumin as an oral therapy has been limited due to its poor aqueous solubility, fixed chemical stability, and low bioavailability. In an attempt to overcome these limitations, we developed curcumin-loaded mixed polymeric micelles. Diabetes mellitus is a most common chronic carbohydrate metabolic disorder. The results clearly demonstrated the ability of developed formulation to reduce the elevated blood glucose level and lipid profile (total cholesterol, triglycerides). It maintained the body-weight, HDL cholesterol level, various biochemical parameters and accelerated the wound healing process when treated with these curcumin-based formulations. The treatment of curcumin loaded mixed polymeric formulations allowed a favorable inhibitory effect to these histopathological changes of liver, kidney, and pancreas. The newly developed curcumin-based formulations have proved superior therapeutic potential and excellent healing efficacy as compared to standard drugs and pure curcumin.
Asunto(s)
Alginatos/química , Quitosano/química , Curcumina/química , Poloxaleno/química , Poloxámero/química , Polisacáridos/química , Cicatrización de Heridas/efectos de los fármacos , Animales , Disponibilidad Biológica , Glucemia/metabolismo , Curcumina/farmacocinética , Curcumina/farmacología , Curcumina/uso terapéutico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/patología , Portadores de Fármacos/química , Hipoglucemiantes/química , Hipoglucemiantes/farmacocinética , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/patología , Micelas , Polisorbatos/química , RatasRESUMEN
Curcumin is a naturally occurring constituent of turmeric that is a good substitute for synthetic medicines for the treatment of different diseases, due to its comparatively safer profile. However, there are certain shortcomings that limit its use as an ideal therapeutic agent. In order to overcome these drawbacks, we prepared novel curcumin-loaded mixed polymeric micelles using different biocompatible polymers by the thin-film hydration method. We investigated the critical micelle concentration and temperature, drug loading and encapsulation efficiency, and minimum inhibitory concentration by spectrophotometry. Surface morphology, stability, particle size, drug-polymer interaction, and physical state of the prepared formulations were investigated using scanning electron microscopy, zeta potential, particle size analyzer, Fourier-transform infrared spectroscopy, and X-ray diffraction, respectively. The drug loading and entrapment efficiency were significantly increased (P < 0.01) when curcumin was encapsulated with pluronic-based mixed polymeric micelles as compared to that of pluronic-based micelles alone. In vitro studies exhibited that pluronic-based mixed polymeric micelles significantly increased anticancer (P < 0.01), antimicrobial (P < 0.001), antioxidant (P < 0.001), and α-amylase inhibitory (P < 0.001) activities when compared to pure curcumin and/or pluronic-based micelles alone. These findings suggest that the formation of mixed polymeric micelles increases the stability and solubility of curcumin.
Asunto(s)
Curcumina/química , Portadores de Fármacos/química , Micelas , Poloxámero/química , Polímeros/química , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/metabolismo , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antineoplásicos/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Curcumina/administración & dosificación , Curcumina/metabolismo , Relación Dosis-Respuesta a Droga , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/metabolismo , Excipientes/administración & dosificación , Excipientes/química , Excipientes/metabolismo , Células HeLa , Humanos , Tamaño de la Partícula , Poloxámero/administración & dosificación , Poloxámero/metabolismo , Polímeros/administración & dosificación , Polímeros/metabolismo , Solubilidad , Difracción de Rayos X/métodosRESUMEN
Traditionally, many natural medicinal plants have been used to treat a variety of diseases since ancient times and are considered a potential source of phytochemicals for the development of new drugs. One of these is curcumin, which is an easily accessible, inexpensive, and nontoxic bioactive compound. Curcumin is a very important, naturally occurring, and highly lipophilic and phenolic substance derived from the rhizomes of plant Curcuma longa, a member of the Zingiberaceae (ginger) family, which is mostly used as a curry spice, flavoring agent, insect repellent, coloring agent in food, traditional drug, and ingredient in cosmetics. Modern scientific research has demonstrated that it has wide range of pharmacological activities and medicinal properties against various types of diseases, disorders, and syndromes. Because it has been known for many years to have excellent therapeutic potential against various diseases, much research has been devoted to this natural product. This review briefly summarizes the scope, therapeutic potential and clinical applications of curcumin.
Asunto(s)
Curcumina/uso terapéutico , Medicina de Hierbas , HumanosRESUMEN
Cancer is found to be the leading cause of death worldwide characterized by uncontrolled cell division. Nuclear medicines imaging using radiopharmaceuticals have pronounced potential for the diagnosis and treatment of cancers. Cyclophosphamide (CPH) is an antineoplastic drug which targets selectively cancer cells. In the present work, labeling of CPH with Tc-99m is performed for diagnostic purpose, which gave labeling yield as high as 99% using 20 µg SnCl2 ·2H2 O, 200 µg of ligand at pH 7 for 10 min reaction time at room temperature. The characterization of the prepared complex was performed using ITLC, electrophoresis, and HPLC. In vitro stability was analyzed in the presence of human serum at 37°C which has maximum value of 94 ± 0.5. The biodistribution studies of 99m Tc-CPH were performed in normal and tumor bearing Swiss Webster mice. The high accumulation of 99m Tc-CPH was observed in liver and tumours respectively at 4 hr after injection. Biodistribution results revealed that 99m Tc-CPH may be a potential tumour diagnostic agent simultaneously with chemotherapy.
Asunto(s)
Antineoplásicos/química , Ciclofosfamida/química , Radiofármacos/síntesis química , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Línea Celular Tumoral , Ciclofosfamida/administración & dosificación , Ciclofosfamida/farmacocinética , Estabilidad de Medicamentos , Semivida , Humanos , Concentración de Iones de Hidrógeno , Inyecciones Intravenosas , Ratones , Radiofármacos/sangre , Tecnecio/química , Distribución Tisular , Trasplante Heterólogo , Imagen de Cuerpo EnteroRESUMEN
Kanamycin is an antibiotic, isolated from Streptomyces kanamyceticus, which is used to treat serious bacterial infections. The fact that the present radioligand 99m Tc-kanamycin used for diagnosis is short-lived, raised a need to label and study kanamycin with one of the most important beta (ß) radiation emitting isotope 177 Lu. Labeling yield of 177 Lu-kanamycin was confirmed by different chromatography techniques such as paper chromatography, TLC, HPLC. Several experiments were performed to optimize labeling with changing reaction conditions such as pH, temperature, amount of ligand, and reaction time. In vitro stability analysis was performed incubation with human serum. Electrophoresis analysis was also conducted to determine the charge on 177 Lu-kanamycin. The biodistribution and scintigraphy were performed in normal mice and rabbit, respectively, at different time intervals of postinjection. 177 Lu-kanamycin was prepared with very high yield (~100%), with excellent stability in vivo and in vitro (>99% 6 hr postprep.), at pH 7. Maximum labeling was achieved at less reaction time (15 min), with maximum conjugation of the ligand (12.5 mg) with 177 Lu. Electrophoresis analysis showed net neutral charge. The radioligand showed rapid clearance from body in biodistribution and scintigraphy studies. The preparation 177 Lu-kanamycin could be used as a radio-pharmaceutical for infection imaging purpose, especially when transporting the radioligand to long-range distances.