RESUMO
Skin cancer can be detected through visual screening and skin analysis based on the biopsy and pathological state of the human body. The survival rate of cancer patients is low, and millions of people are diagnosed annually. By determining the different comparative analyses, the skin malignancy classification is evaluated. Using the Isomap with the vision transformer, we analyze the high-dimensional images with dimensionality reduction. Skin cancer can present with severe cases and life-threatening symptoms. Overall performance evaluation and classification tend to improve the accuracy of the high-dimensional skin lesion dataset when completed. In deep learning methodologies, the distinct phases of skin malignancy classification are determined by its accuracy, specificity, F1 recall, and sensitivity while implementing the classification methodology. A nonlinear dimensionality reduction technique called Isomap preserves the data's underlying nonlinear relationships intact. This is essential for the categorization of skin malignancies, as the features that separate malignant from benign skin lesions may not be linearly separable. Isomap decreases the data's complexity while maintaining its essential characteristics, making it simpler to analyze and explain the findings. High-dimensional datasets for skin lesions have been evaluated and classified more effectively when evaluated and classified using Isomap with the vision transformer.
Assuntos
Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/classificação , Neoplasias Cutâneas/diagnóstico , Aprendizado Profundo , Pele/patologiaRESUMO
Millions of people are affected by neurodegenerative diseases worldwide. They occur due to the loss of brain functions or peripheral nervous system dysfunction. If untreated, prolonged condition ultimately leads to death. Mostly they are associated with stress, altered cholesterol metabolism, inï¬ammation and organelle dysfunction. Endogenous cholesterol and phospholipids in brain undergo auto-oxidation by enzymatic as well as non-enzymatic modes leading to the formation of by-products such as 4-hydroxynonenal and oxysterols. Among various oxysterols, 7-ketocholesterol (7KCh) is one of the major toxic components involved in altering neuronal lipid metabolism, contributing to inï¬ammation and nerve cell damage. More evidently 7KCh is proven to induce oxidative stress and affects membrane permeability. Loss in mitochondrial membrane potential affects metabolism of cell organelles such as lysosomes and peroxisomes which are involved in lipid and protein homeostasis. This in turn could affect amyloidogenesis, tau protein phosphorylation and accumulation in pathological conditions of neurodegenerative diseases. Lipid alterations and the consequent pathogenic protein accumulation, results in the damage of cell organelles and microglial cells. This could be a reason behind disease progression and predominantly reported characteristics of neurodegenerative disorders such as Alzheimer's disease. This review focuses on the role of 7KCh mediated neurodegenerative Alzheimer's disease with emphasis on alterations in the lipid raft microdomain. In addition, current trends in the significant therapies related to 7KCh inhibition are highlighted.
Assuntos
Doença de AlzheimerRESUMO
PURPOSE: To investigate the expression of αA- and αB-crystallin and heat shock protein 70 (Hsp 70) during curcumin treatment of selenium-induced cataractogenesis in Wistar rat pups. METHODS: Group I Wistar rat pups received only saline and served as the control. Group II Wistar rat pups were intraperitoneally injected with selenium (15 µM/kg bodyweight) to induce cataract. Group III Wistar rat pups also underwent selenium-induced cataract but were cotreated with 75 mg/kg body weight of curcumin (single oral dose). Group IV Wistar rat pups with selenium-induced cataract were post-treated with curcumin at the group III dosage 24 h after selenium administration. Group V Wistar rat pups with selenium-induced cataract were pretreated with curcumin at the group III dosage 24 h before selenium administration. RESULTS: This study found higher levels of αA- and αB-crystallin and Hsp 70 in lenses injected with selenium alone (group II) than in control lenses (group I). Similar results were observed in the group III and IV lenses. In contrast, in group V, the presence of curcumin 24 h before selenium injection decreased the αA- and αB-crystallin and Hsp 70 levels to almost the same as those found in group I lenses. CONCLUSIONS: Curcumin suppressed the expression of selenite-induced αA- and αB-crystallin and Hsp 70, and may therefore suppress cataract formation in rat pups.
Assuntos
Catarata/metabolismo , Curcumina/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Selênio/farmacologia , Cadeia A de alfa-Cristalina/metabolismo , Cadeia B de alfa-Cristalina/metabolismo , Animais , Western Blotting , Peso Corporal , Catarata/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Imuno-Histoquímica/métodos , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Selenito de Sódio/farmacologiaRESUMO
Racial differences in outcomes are well known in children after heart transplant (HT) but not in children awaiting HT. We assessed racial and ethnic differences in wait-list mortality in children <18 years old listed for primary HT in the United States during 1999-2006 using multivariable Cox models. Of 3299 listed children, 58% were listed as white, 20% as black, 16% as Hispanic, 3% as Asian and 3% were defined as 'Other'. Mortality on the wait-list was 14%, 19%, 21%, 17% and 27% for white, black, Hispanic, Asian and Other children, respectively. Black (hazard ratio [HR] 1.6, 95% confidence interval [CI] 1.3, 1.9), Hispanic (HR 1.5, CI 1.2, 1.9), Asian (HR, 2.0, CI 1.3, 3.3) and Other children (HR 2.3, CI 1.5, 3.4) were all at higher risk of wait-list death compared to white children after controlling for age, listing status, cardiac diagnosis, hemodyamic support, renal function and blood group. After adjusting additionally for medical insurance and area household income, the risk remained higher for all minorities. We conclude that minority children listed for HT have significantly higher wait-list mortality compared to white children. Socioeconomic variables appear to explain a small fraction of this increased risk.
Assuntos
Etnicidade , Cardiopatias Congênitas/mortalidade , Transplante de Coração , Grupos Raciais , Listas de Espera , Sistema ABO de Grupos Sanguíneos , Adolescente , Negro ou Afro-Americano , Povo Asiático , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Transplante de Coração/mortalidade , Hispânico ou Latino , Humanos , Lactente , Masculino , Grupos Minoritários , Análise Multivariada , Modelos de Riscos Proporcionais , Fatores Socioeconômicos , Estados Unidos , População BrancaRESUMO
The presence of xenobiotic contaminants especially metals in coastal waters is a major concern as they are immunotoxic to aquatic animals even at low concentrations. In our present study, mud crab Scylla serrata was exposed to three sublethal concentrations (0.4, 0.6 and 0.8 mg/L) of nickel for 30 days under laboratory conditions and the alterations of hematological parameters like haemocyte count, clotting time, haemocyte viability, protein content and immunomodulatory components like phenoloxidase, phagocytosis and superoxide anion generation were measured. In addition, the accumulation patterns of nickel were measured in gills, hepatopancreas and ovary. The accumulation was more in gills when compared to hepatopancreas and ovary of crabs exposed to nickel and was not detected in the control crabs. The results revealed a significant (P<0.05) induction of superoxide anion generation and phagocytosis activity in the haemolymph of the crabs exposed to nickel when compared to control. On the contrary, the rest of the parameters were significantly (P<0.05) reduced in the experimental groups when compared to the control. All the studied parameters exhibited a concentration dependent response.
Assuntos
Braquiúros/efeitos dos fármacos , Braquiúros/imunologia , Imunotoxinas/toxicidade , Níquel/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Sistema Imunitário/efeitos dos fármacos , Dose Letal MedianaRESUMO
This study investigated the potential of vitamin K1 as a novel lens aldose reductase inhibitor in a streptozotocin-induced diabetic cataract model. A single, intraperitoneal injection of streptozotocin (STZ) (35 mg/kg) resulted in hyperglycemia, activation of lens aldose reductase 2 (ALR2) and accumulation of sorbitol in eye lens which could have contributed to diabetic cataract formation. However, when diabetic rats were treated with vitamin K1 (5 mg/kg, sc, twice a week) it resulted in lowering of blood glucose and inhibition of lens aldose reductase activity because of which there was a corresponding decrease in lens sorbitol accumulation. These results suggest that vitamin K1 is a potent inhibitor of lens aldose reductase enzyme and we made an attempt to understand the nature of this inhibition using crude lens homogenate as well as recombinant human aldose reductase enzyme. Our results from protein docking and spectrofluorimetric analyses clearly show that vitamin K1 is a potent inhibitor of ALR2 and this inhibition is primarily mediated by the blockage of DL-glyceraldehyde binding to ALR2. At the same time docking also suggests that vitamin K1 overlaps at the NADPH binding site of ALR2, which probably shows that vitamin K1 could possibly bind both these sites in the enzyme. Another deduction that we can derive from the experiments performed with pure protein is that ALR2 has three levels of affinity, first for NADPH, second for vitamin K1 and third for the substrate DL-glyceraldehyde. This was evident based on the dose-dependency experiments performed with both NADPH and DL-glyceraldehyde. Overall, our study shows the potential of vitamin K1 as an ALR2 inhibitor which primarily blocks enzyme activity by inhibiting substrate interaction of the enzyme. Further structural studies are needed to fully comprehend the exact nature of binding and inhibition of ALR2 by vitamin K1 that could open up possibilities of its therapeutic application.
Assuntos
Aldeído Redutase/genética , Catarata/tratamento farmacológico , Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Vitamina K 1/farmacologia , Animais , Glicemia/efeitos dos fármacos , Catarata/genética , Catarata/patologia , Complicações do Diabetes/genética , Complicações do Diabetes/patologia , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Modelos Animais de Doenças , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/genética , Hiperglicemia/patologia , Cristalino/efeitos dos fármacos , Cristalino/patologia , Oxirredução/efeitos dos fármacos , Ratos , Vitamina K 1/metabolismoRESUMO
OBJECTIVE: To describe the clinical and laboratory features of a painful non-length dependent, small fibre ganglionopathy (SFG). BACKGROUND: The syndrome of generalised SFG with early involvement of the face, trunk or proximal limbs is not well recognised and contrasts with the burning feet syndrome of small fibre neuropathy (SFN) and classical large fibre features of sensory ganglionopathy. METHODS: Retrospective case review including skin biopsies from four neuromuscular centres. Patients with pre-existing diseases associated with ganglionopathies were excluded. RESULTS: 12 men and 11 women, with an average age of 50 years, were studied. Neuropathic pain developed over days in eight and over months in the other patients. The face (n = 12), scalp (n = 10), tongue (n = 6), trunk (n = 15) and acral extremities (n = 21) were involved. Symptoms began in the hands or face before the legs in 10. The pain was characterised as burning (n = 22), prickling (n = 13), shooting (n = 13) or allodynic (n = 11). There was loss of pinprick sensation in affected regions in 19, with minimal or no loss of large fibre sensibility. Laboratory findings included abnormal glucose metabolism in six patients, Sjögren syndrome in three and monoclonal gammopathy, sprue and hepatitis C infection in one each, with the remainder idiopathic. Sensory nerve action potentials were normal in 12 and were reduced in the hands but normal in the legs in six. Skin biopsy in 14 of 17 showed reduced nerve fibre density in the thigh equal to or more prominent than in the calf. Two of seven patients improved with immune therapies, 13 symptomatically with analgesic medications and the remainder had little improvement. Ten considered the pain disabling at the last follow-up (mean 2 years). CONCLUSION: The pattern of symmetric, non-length dependent neuropathic pain with face and trunk involvement suggests a selective disorder of the dorsal ganglia cells subserving small nerve fibres. It can be distinguished from distal SFN. A potential metabolic or immune process was detected in half of the cases and the disorder was often refractory to treatment.
Assuntos
Gânglios Espinais/fisiopatologia , Fibras Nervosas/fisiologia , Neuralgia/fisiopatologia , Adulto , Idoso , Sistema Nervoso Autônomo/patologia , Sistema Nervoso Autônomo/fisiopatologia , Biópsia , Contagem de Células , Extremidades/inervação , Dor Facial/tratamento farmacológico , Dor Facial/etiologia , Dor Facial/patologia , Dor Facial/fisiopatologia , Feminino , Seguimentos , Gânglios Espinais/patologia , Humanos , Imunização Passiva , Masculino , Metilprednisolona/administração & dosagem , Microscopia Eletrônica , Pessoa de Meia-Idade , Neurônios Motores/patologia , Neurônios Motores/fisiologia , Fibras Nervosas/patologia , Fibras Nervosas Amielínicas/patologia , Fibras Nervosas Amielínicas/fisiologia , Condução Nervosa/fisiologia , Neuralgia/diagnóstico , Neuralgia/tratamento farmacológico , Neuralgia/patologia , Neurônios/patologia , Neurônios/fisiologia , Neurônios Aferentes/patologia , Neurônios Aferentes/fisiologia , Medição da Dor , Nervos Periféricos/patologia , Nervos Periféricos/fisiopatologia , Prednisona/administração & dosagem , Estudos Retrospectivos , Pele/inervação , Nervo Sural/patologiaRESUMO
OBJECTIVE: The aim of this study was to understand the mechanism of action of vitamin K1 against streptozotocin (STZ)-induced diabetes. METHODS: Male Wistar rats were administered 35 mg/kg STZ and after 3 d were treated with vitamin K1 (5 mg/kg, twice a week) for 3 months. Blood glucose was monitored twice a month. At the end of the study, animals were sacrificed and pancreas dissected out and analyzed for free radicals, antioxidants, metabolic enzymes related to glucose, membrane ATPases, histopathological evaluation, and expression of nuclear factor (NF)-κB and inducible nitric oxide synthase (iNOS). Glycated hemoglobin, plasma insulin, and islet area were determined at the end of the study. RESULTS: Treatment of STZ-induced type 1 diabetic rats with vitamin K1 reduced oxidative stress, enhanced antioxidants, and inhibited aldose reductase in pancreas. Vitamin K1 administration rescued endocrine pancreas from STZ-induced cell death, resulting in enhanced insulin secretion and normal blood glucose and glycosylated hemoglobin levels. Histologic analyses also showed the antidiabetic potential of vitamin K1. Measure of pancreatic islet area showed an increase in the islet area upon vitamin K1 treatment when compared with the STZ-administered group, suggesting the possibility of regeneration. To understand the mechanism involved in vitamin K1 mediated changes, we performed immunohistochemical analyses for NF-κB and iNOS enzyme. Vitamin K1 was shown to suppress NF-κB activation and iNOS expression in the islets upon administration of STZ. CONCLUSION: This work shows, to our knowledge for the first time, the mechanism of action of vitamin K1 against type 1 diabetes and the possible therapeutic use of this vitamin in stimulating islet cell proliferation/regeneration.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , NF-kappa B/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Vitamina K 1/farmacologia , Animais , Antioxidantes/farmacologia , Glicemia/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/tratamento farmacológico , Relação Dose-Resposta a Droga , Hemoglobinas/metabolismo , Hipoglicemiantes/farmacologia , Insulina/sangue , Insulina/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Masculino , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Ratos , Ratos Wistar , Estreptozocina/efeitos adversosRESUMO
Chemical transformations of metal nanoparticles can be an important way to mitigate nanoparticle toxicity. Sulfidation of silver nanoparticle (AgNPs) is a natural process shown to occur in environment. Very few studies, employing microbes and embryonic stages of zebrafish, have shown reduction in AgNPs toxicity as a direct result of sulfidation. However the feasibility of reducing nanoparticle toxicity by sulfidation of AgNPs has never been studied in adult vertebrates. In this study, we have used adult zebrafish as a model to study the efficacy of sulfidation of AgNPs in reducing nanoparticle toxicity by employing a battery of biomarkers in liver and brain. While AgNPs enhanced liver oxidative stress, altered detoxification enzymes and affected brain acetylcholinesterase activity, sulfidation of AgNPs resulted in significant alleviation of changes in these parameters. Histopathological analyses of liver and sulphydryl levels also support the significance of sulfidated AgNPs in controlling the toxicity of AgNPs. Our study provides the first biochemical data on the importance of sulfidation of AgNPs in reducing biological toxicity in adult vertebrates.
Assuntos
Fígado/efeitos dos fármacos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Prata/química , Prata/toxicidade , Sulfetos/química , Peixe-Zebra/fisiologia , Animais , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidadeRESUMO
Reperfusion of ischemic tissue is associated with an acute inflammatory response that may further exacerbate vascular and tissue damage. Compelling evidence from a variety of animal models indicates that neutrophils are the principle effector cells of the reperfusion injury and that blockade of neutrophil adhesion to endothelium attenuates ischemia-reperfusion injury. "Anti-adhesion" therapy may represent a new approach to treatment of the many diverse clinical disorders in which ischemia-reperfusion occurs.
Assuntos
Moléculas de Adesão Celular/fisiologia , Endotélio Vascular/fisiologia , Leucócitos/fisiologia , Traumatismo por Reperfusão/fisiopatologia , Selectinas/fisiologia , Animais , Humanos , Imunoglobulinas/fisiologia , Integrinas/fisiologia , Neutrófilos/fisiologia , Traumatismo por Reperfusão/sangueRESUMO
OBJECTIVE: We sought to examine the effects of modified venovenous ultrafiltration after cardiopulmonary bypass on pulmonary compliance in infants. METHODS: We prospectively enrolled 38 infants undergoing their first operation for congenital heart disease. Infants were randomized to receive 20 minutes of modified ultrafiltration after bypass or control. Static and dynamic compliance was measured after induction of anesthesia, before and immediately after filtration in the operating theater, 1 hour after return to the pediatric intensive care unit, and 24 hours after the operation. Length of time on the ventilator, inotropic requirements, and length of stay in the intensive care unit were recorded. RESULTS: Modified ultrafiltration produced a significant immediate improvement in dynamic (pre-ultrafiltration 2.5 +/- 1.9 mL/cm H(2)O to post-ultrafiltration 2.9 +/- 2.7 mL/cm H(2)O, P =.03) and static (pre-ultrafiltration 2.1 +/- 0.9 mL/cm H(2)O to post-ultrafiltration 2.9 +/- 2.1 mL/cm H(2)O, P =.04) compliance. However, there was no significant difference in the change in dynamic (P =.3) or static (P =.7) compliance in the ultrafiltration and control groups when compared before the operation, after the operation, and at 24 hours. There was no significant difference in the time to extubation between patients and control subjects (140 +/- 91 hours vs 90 +/- 58 hours) or the length of intensive care unit stay (10.0 +/- 9.1 days vs 7.4 +/- 5.7 days). CONCLUSIONS: Modified ultrafiltration produces an improvement in pulmonary compliance after bypass in infants. However, these improvements are not sustained past the immediate post-ultrafiltration period and do not lead to a decreased length of intubation or intensive care unit stay.
Assuntos
Ponte Cardiopulmonar , Cardiopatias Congênitas/cirurgia , Hemofiltração/métodos , Complacência Pulmonar/fisiologia , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/fisiopatologia , Humanos , Lactente , Recém-Nascido , Estudos ProspectivosRESUMO
BACKGROUND: Peripherally inserted central venous catheters (PICCs) are commonly used intravenous access devices in children. Although PICCs are intended to be placed in central veins, many fail to reach this location. These noncentral PICCs are used for administration of medications and isotonic solutions. OBJECTIVES: To examine the efficacy of noncentral PICCs for completion of therapy, the complications associated with their use, and the effectiveness of noncentral PICCs as compared with PICCs placed in a central vein. DESIGN: A prospective cohort study of children in whom PICCs were inserted, from January 1, 1994, to January 1, 1996. SETTING: A university-affiliated teaching institution. MAIN OUTCOME MEASUREMENT: Completion of intravenous therapy. RESULTS: A total of 587 PICCs were studied. Thirty-nine percent of PICCs were placed in noncentral veins. Centrally placed PICCs had significantly longer catheter duration compared with those placed noncentrally (16.6 vs 11.4 days, respectively). However, central and noncentral PICCs had similar therapy completion rates (73% and 69%, respectively). Catheter failure because of occlusion and accidental dislodgment were similar for central and noncentral PICCs. Likewise, complications caused by exit-site infection, phlebitis, and catheter-associated sepsis were also similar for catheters in the 2 locations. Catheter survival curves were similar for central and noncentral PICCs. CONCLUSIONS: Our study demonstrates that PICCs placed in noncentral veins provide reliable and safe intravenous access for administration of many medications and isotonic solutions for about 2 weeks' duration. The placement of PICCs in central veins may be restricted to those children who need central vascular access because of the type of intended therapy.
Assuntos
Cateterismo Venoso Central/métodos , Cateterismo Periférico , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/instrumentação , Criança , Pré-Escolar , Falha de Equipamento , Estudos de Avaliação como Assunto , Humanos , Lactente , Recém-Nascido , Estudos Prospectivos , Fatores de RiscoRESUMO
The compound was isolated from leaves of Cassia auriculata and its structure was characterized using high-performance liquid chromatography (HPLC), liquid chromatography mass spectrometry (LC-MS), UV-vis spectroscopy (UV-vis), fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, cytotoxicity, nuclear morphology and lactate dehydrogenase assay of isolated compound was tested against human colon cancer cell line HCT 15. The isolated compound, 4-(4-chlorobenzyl)-2,3,4,5,6,7-hexahydro-7-(2-ethoxyphenyl)benzo[h][1,4,7]triazecin-8(1H)-one at 25µg/ml concentration and by 48h showed 50% inhibition of human colon cancer cells (HCT 15). The results suggest that isolated compound from C. auriculata has potential to prevent colon cancer cell line.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Cassia/química , Neoplasias do Colo/prevenção & controle , Anticarcinógenos/química , Anticarcinógenos/isolamento & purificação , Anticarcinógenos/farmacologia , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , HumanosRESUMO
A compound was isolated from Cassia auriculata leaves and characterized by high-performance liquid chromatography (HPLC), liquid chromatography mass spectrometry (LC-MS), UV-vis spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). The in vitro anticancer effect of the compound isolated from C. auriculata was evaluated in human colon cancer cells HCT 15 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cytotoxicity, nuclear morphology analysis and measurement of lactate dehydrogenase. The isolated compound 4-(2,5 dichlorobenzyl)-2,3,4,5,6,7 hexahydro7(4 methoxyphenyl)benzo[h][1,4,7] triazecin8(1H)-one showed 50% inhibition of HCT 15 cells when tested at 20µg/ml after 24h incubation. Cytotoxicity, nuclear morphology and lactate dehydrogenase assays clearly show potent anticancer activity of the isolated compound against colon cancer. Thus, the in vitro findings suggest that the compound isolated from C. auriculata leaves have potent anti-cancer properties with possible clinical applications.
Assuntos
Antineoplásicos Fitogênicos , Apoptose/efeitos dos fármacos , Cassia/química , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Folhas de Planta/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , HumanosRESUMO
INTRODUCTION: Banking of high-quality placental tissue specimens will enable biomarker discovery and molecular studies on diseases involving placental dysfunction. Systematic studies aimed at developing feasible standardized methodology for placental collection in a typical clinical setting are lacking. METHODS: To determine the acceptable timeframe for placental collection, we collected multiple samples from first and third trimester placentas at serial timepoints in a 2-h window after delivery, simultaneously comparing the traditional snap-freeze technique to commercial solutions designed to preserve RNA (RNAlater™), and DNA (DNAgard(®)). The performance of RNAlater for preserving DNA was also tested. Nucleic acid quality was assessed by determining the RNA integrity number (RIN) and genome-wide microarray profiling for gene expression and DNA methylation. RESULTS: We found that samples collected in RNAlater had higher and more consistent RINs compared to snap-frozen tissue. Similar RINs were obtained for tissue collected in RNAlater as large (1 cm(3)) and small (â¼0.1 cm(3)) pieces. RNAlater appeared to better stabilize the time zero gene expression profile compared to snap-freezing for first trimester placenta. DNA methylation profiles remained quite stable over a 2 h time period after removal of the placenta from the uterus, with DNAgard being superior to other treatments. DISCUSSION AND CONCLUSION: The collection of placental samples in RNAlater and DNAgard is simple, and eliminates the need for liquid nitrogen or a freezer on-site. Moreover, the quality of the nucleic acids and the resulting data from samples collected in these preservation solutions is higher than samples collected using the snap-freeze method and easier to implement in busy clinical environments.
Assuntos
Placenta , Manejo de Espécimes , Bancos de Tecidos , Metilação de DNA , Feminino , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Genômica , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Terceiro Trimestre da Gravidez , RNA Mensageiro/análiseRESUMO
The major causes for cataract formation are free radicals, and these free radicals are neutralized by the presence of endogenous antioxidants in the eye. Using xenobiotics, it has been confirmed that free radicals mediate the formation of cataract. Two cataract model-selenite model and the diabetic cataract model-have been developed to study the pathophysiology of cataract formation due to free radicals and the role of antioxidants during the process of cataractogenesis. This review focuses on natural compounds with antioxidant properties that could actually be applied as an interventional strategy on a large scale and are also relatively inexpensive. A brief overview of plants with antioxidant properties that in addition possess potential anti-cataract properties has been discussed. In addition to plants, three natural compounds (curcumin, vitamin C and vitamin E), on which a lot of data exist showing anti-cataract and antioxidant activities, have also been discussed. These antioxidants can be supplemented in the diet for a better defence against free radicals. Studies on vitamin C and vitamin E have proved that they are capable of preventing lipid peroxidation, thereby preventing the generation of free radicals, but their efficacy as anti-cataract agent is questionable. Unlike vitamins C and E, curcumin is well established as an anti-cataract agent, but the issue of curcumin bioavailability is yet to be addressed. Nanotechnology proves to be a promising area in increasing the curcumin bioavailability, but still a lot more research needs to be done before the use of curcumin as an effective anti-cataract agent for humans.
Assuntos
Antioxidantes/administração & dosagem , Catarata/tratamento farmacológico , Suplementos Nutricionais , Cristalino/patologia , Antioxidantes/metabolismo , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/metabolismo , Catarata/metabolismo , Catarata/patologia , Curcumina/administração & dosagem , Curcumina/metabolismo , Radicais Livres/administração & dosagem , Radicais Livres/metabolismo , Humanos , Cristalino/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Vitamina E/administração & dosagem , Vitamina E/metabolismoRESUMO
The aim of the study was to develop a new strategy for the differentiation of hematopoietic stem cell (HSC) derived from UCB into hepatocyte like cells and also to estimate the effects of combination of fibroblast growth factor 4 (FGF 4) and hepatocyte growth factor (HGF) on hematopoietic stem cell differentiation. HSCs were isolated and purified by magnetic activated cell sorting. HSCs were induced to hepatocyte like cells under a 2-step protocol with combination of growth factors. Reverse transcription polymerase chain reaction was performed to detect multiple genes related to hepatocyte like cells development and function. Hepatocyte like morphology was illustrated by inverted repeat microscope and the secretion of albumin and α- fetoprotein by these cells was confirmed by enzyme linked immunosorbent assay. Hepatocyte like cells was observed at the end of the protocol (days 14). These differentiated cells were observed to show high expression of genes related to hepatocytes (tryptophan 2, 3-dioxygenase [TO], glucose 6-phosphate [G6P], cytokeratin 18 [CK 18], albumin and α- fetoprotein [AFP]). The quantities of albumin and AFP at day 0 were low and upon differentiation the cells were able to produce albumin and AFP at high levels. Our results show a new strategy for differentiation in a short duration, using a combination of growth factors for the differentiation of umbilical cord blood derived HSC into hepatocyte like cells under certain in vitro conditions. After further studies this approach has the potency, for widespread cell replacement therapy for liver diseases.
RESUMO
PURPOSE: The present study was aimed at investigating the possible antioxidant potential of curcumin at a dose of 75 mg/kg body weight on selenite-induced cataract in experimental rat pups. METHODS: Group I: Control rat pups receiving physiological saline; Group II: Selenite-induced group (15 microM/kg body wt); Group III: Selenite-induced group co-treated with curcumin (single dose of curcumin orally 75 mg/kg body wt); Group IV: Selenite-induced animals post-treated (after 24 hrs) with curcumin at a dose mentioned for group III; Group V: Rat pups were pretreated with curcumin (dose as mentioned in Group III), 24 hrs before the administration of selenite. Encapsulated lenses liver, kidney, and serum were analyzed for antioxidant enzymes and malondialdehyde, a marker of lipid peroxidation. RESULTS: Intraperitoneal injection of sodium selenite (15 microM/kg body wt) to 8-10-day-old rat pups led to severe oxidative stress in eye lens as evidenced by enhanced LPO levels that led to cataract formation. Sodium selenite also led to decrease in activities of SOD, GST, GPx, CAT with simultaneous decrease in the levels of GSH, vitamin C, and vitamin E. Treatment with curcumin (75 mg/kg body wt) led to a significant decrease in the levels of LPO, enzymic antioxidants, and nonenzymic antioxidants, which were similar to that of control. CONCLUSIONS: Curcumin suppressed selenite-induced oxidative stress and cataract formation in rat pups. The presence of oxidative stress in selenite cataract development and its prevention by curcumin support the possibility that the natural consumption of curcumin in food can help prevent the onset of senile cataract.