ABSTRACT
Leukemia is a blood disease that creates from inhibition of differentiation and increased proliferation rate. The nature has been known as a rich source of medically useful substances. High diversity of bioactive molecules, extracted from marine invertebrates, makes them as ideal candidates for cancer research. The study has been done to investigate cytotoxic effects of dichloromethane brittle star extract and doxorubic in on EL4 cancer cells. Blood cancer EL4 cells were cultured and treated at different concentrations of Brittle Star [Ophiocoma erinaceus] dichloromethane extract at 24, 48 and 72 h. Cell toxicity was studied using MTT assay. Cell morphology was examined using an invert microscope. Further, apoptosis was examined using Annexin V-FITC, propodium iodide, DAPI, and Acridine orange/propodium iodide staining. Eventually, the apoptosis pathways were analyzed using measurement of Caspase 3 and 9 activity. The statistical analysis was performed using SPSS, ANOVA software, and Tukey's test. P < 0.05 was considered to be significant. MTT assay and morphological observations showed that dichloromethane extract can inhibit cell growth in a dose dependent. The results considered 32 micro g/mL of the extract as IC[50]. Also, doxorubicin suppressed EL4 proliferation as IC[50]= 32 micro g/mL. All experiments related to apoptosis analysis confirmed that dichloromethane Brittle Star extract and doxorubic in have a cytotoxic effect on EL4 cells in IC[50] concentration. The study showed that dichloromethane Brittle Star extract is as an adjunct to doxorubicin in treatment of leukemia cells
ABSTRACT
Ophiocoma erinaceus Muller and Troschel [Ophiocomidae] is part of the extensive group of echinoderm that contains bioactive metabolites. As the anti cancer potential of brittle star saponin has not been reported against cervical cancer, the present study was conducted to evaluate the anticancer effect of extracted crude saponin. Saponin extraction was conducted using conventional method such as froth test, TLC, FTIR and erythrolysis assay. The Hela-S3 cervical carcinoma and HNCF-PI52 normal cells were treated with different concentrations of saponin fraction for 24 and 48 h. The cytotoxicity was examined by MTT, DAPI, AO/PI, Annexin V-FITC and flow cytometry. In addition, the apoptotic induced pathway was studied using caspase assay, evaluation of ROS generation and Bcl-2 mRNA level. Crude saponin showed cytotoxic properties in Hela-S3 cells [IC[50] of 23.4 micro g/mL] without significant impact against normal cells. In addition, the crude saponin increased sub-G1 peak in flow cytometry histogram of treated cells, ROS generation and caspase-3 and -9 activity [IC[50] of 11.10, 11.27 micro g/mL]. The dose dependent down regulation of Bcl-2 in treated cells demonstrated that saponin fraction can trigger intrinsic apoptotic pathway in cancer cells. This study provides valuable information about the apoptotic inducing effect of saponin fraction, which can offer new insights into the anticancer potential of saponin as a promising candidate against human cervical carcinoma
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Background: Marine organisms provide appreciable source of novel bioactive compounds with pharmacological potential. There is little information in correlation with anti-cancer activities of brittle star. In the present study, anti-neoplastic efficacy of Ophiocoma erinaceus methanol extract against human cervical cancer cells was investigated
Methods: The HeLa cells were cultured and exposed to brittle star methanol extract for 24 and 48 hr. The anti-proliferative properties were examined by MTT assay and the type of cell death induced was evaluated through morphological changes, flow cytometry, Annexin kit and caspase assay. To assess the anti-metastatic activity, wound healing assay was conducted and photographs were taken from the scratched areas. Further, to understand molecular mechanism of cell apoptosis, the expression of Bax was evaluated
Results: The morphological analysis and MTT assay exhibited that the brittle star methanol extract can exert dose dependent inhibitory effect on cells viability [IC[50], 50 Mu g/ml]. Flow cytometry and fluorescence microscopy demonstrated increment of sub-G1 peak, early and late apoptosis in HeLa treated cells. Wound healing migration assay showed that brittle star extract has anti-neoplastic efficacy by inhibiting cell migration. Caspase assay and RT-PCR analysis revealed that brittle star methanol extract induced caspase dependent apoptosis in HeLa cells through up-regulation of caspase-3 followed by up-regulation of Bax gene which is a hallmark of intrinsic pathway recruitment
Conclusion: These results represented further insights into the chemopreventive potential of brittle star as a valuable source of unknown therapeutic agents against human cervical cancer
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Background: The SALL4/Sall4 is constitutively expressed in human and mice. SALL4 mRNA could be used as a marker for the diagnosis of different types of cancers. On the other hand, chrysin has diverse biological properties
Objectives: In the present study, the effect of the chrysin was investigated on the CT26 colon cancer in vitro and in vivo. Furthermore, the expression levels of the stem cell markers; sall4 and Bax was analyzed, as well
Materials and Methods: The cytotoxic effects and the type of cell death induced by chrysin were evaluated using a number of biological assays. The apoptotic pathway was examined by caspase-3and caspase-9 assay. The in vivo antitumor efficacy of chrysin on transplanted CT26 tumor cells in BALB/c mice was investigated. In addition, mRNA expression of sall4, Bax was analyzed with RT-PCR
Results: MTT assay and morphological characteristics showed that chrysin exerted a cytotoxic effect on CT26 cells in a dose dependent manner with IC[50]= 80 micro g.mL[-1]. The biological assays have indicated that chrysin administrated cytotoxicity on colon cancer cells through recruitment of the apoptosis. Caspase-3 and caspase-9 colorimetric assays, in addition to Bax expression analysis, have indicated the involvement of intrinsic apoptotic pathway in the cytotoxic effect of the chrysin. The in vivo assay revealed a remarkable reduction of the colon tumor volume in treated mice [8, 10 mg.kg [-1]] as compared to the untreated mice. RT-PCR elucidated that chrysin attenuated tumor volume through down regulation of the sall4 and up-regulation of the Bax
Conclusions: It was demonstrated that chrysin accomplishes anti-cancer effect on colon cancer cells via induction of the apoptosis and attenuation of the sall4 the expression. These findings introduce chrysin as an efficient apoptosis based therapeutic agent against colon cancer
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Background: Malignant melanoma is a highly aggressive malignant melanocytic neoplasmwhich resists against the most conventional therapies. Sea cucumber as one ofmarine organisms contains bioactive compounds such as polysaccharide, terpenoidand other metabolites which have anti-cancer, anti-tumor, anti-inflammatory andantioxidant properties. The present study was designed to investigate the anticancerpotential of saponin extracted from sea cucumber Holothuria leucospilata alone andin combination with dacarbazine on B16F10 melanoma cell line
Methods: The B16F10 cell line was treated with different concentrations of saponin [0,4, 8, 12, 16, 20micro g/ml], dacarbazine [0, 1200, 1400, 1600, 1800, 2000micro g/ml] and coadministrationof saponin-dacarbazine [1200 da +8 sp, 1200 da +4 sp] for 24 and 48 hrand the cytotoxic effect was examined by MTT, DAPI, acridine orange/propodium iodide,flow cytometry and caspase colorimetric assay
Results: The results exhibited that sea cucumber saponin, dacarbazine, and coadministrationof saponin-dacarbazine inhibited the proliferation of melanoma cellsin a dose and time dependent manner with IC[50]values of 10, 1400 and 4 +1200micro g/ml,respectively. Morphological observation of DAPI and acridine orange/propodium iodidestaining documented typical characteristics of apoptotic cell death. Flowcytometry assay indicated accumulation of IC[50]treated cells in sub-G1 peak. Additionally,saponin extracted induced intrinsic apoptosis via up-regulation of caspase-3and caspase-9
Conclusion: These results revealed that the saponin extracted from sea cucumber as anatural anti-cancer compound may be a new treatment modality for metastaticmelanoma and the application of sea cucumber saponin in combination withdacarbazine demonstrated the strongest anti-cancer activity as compared with thedrug alone
ABSTRACT
Cancer is the second important reason of mortality in the world. In this regard melanoma was accounted as the most aggressive type of cutaneous cancer. Among drug extracted from natural products from marine organisms have been focused investigations related to chemotherapeutic agents derived from echinoderms such as sea cucumbers and starfish. In the present study, cytotoxic and apoptosis inducing potential of Persian Gulf brittle stars dichloromethane extract were evaluated against melanoma cancers. In this study, anti-proliferative effect of brittle stars dichloromethane extract on B16F10 melanoma cells examined by MTT assay and morphological characterization and death inducing effect of Annexin-PI and PI flow cytometry. The data analysis was performed by SPSS software and p<0.05 were considered significant. The dichloromethane extract of brittle star revealed significant cytotoxic effect on B16F10 melanoma cells with IC[50]= 31 microg/ml which is stronger than inhibitory effect of methanol extract on melanoma cell growth. In addition, brittle star dichloromethane extract recruited apoptotic pathway in the response of 31 microg/ml treatment. This study showed that certain concentrations of dichloromethane brittle stars possess cytotoxic activity that can be used as an anticancer agent used in clinical trial due to cell growth inhibition and apoptosis induction which offer therapeutic investigations of dichloromethane brittle star extract as complementary for melanoma treatment and prevention
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Background and Aim: Brittle star possess bioactive compounds which confer the wound healing capacity and regenerative potency of damaged arms and organisms to this creature. The aim of the current study was to assess the protective effect of the star extract on liver damages induced by carbon tetrachloride in adult male Wistar rats
Materials and Methods: In this experimental study, 32 adult male rats were randomly divided into 4 equal groups: control, Sham exposed, experimental 1 [treated with %25 extract] and experimental 2 [treated with %50 extract] of star Ophiocoma Erinaceus. The control group received no treatment. The sham exposed groups received carbon tetrachloride .[50% in olive oil] .0.5 ml/kg for 7 days. The experimental groups firstly received carbon tetrachloride, then received %25, %50 brittle star extract as intragastric for 7 days
Finally, the animals were sacrificed, and their bodies and livers were weighed. Then, the livers sections were prepared and were examined by means of light microscope. Finally, the obtained quantitative data was analyzed using SPSS [V: 20], Mini Tab software, ANOVA, and Tukey. at the significant level of P<0.001
Results: Carbon tetrachloride significantly decreased the rats' body weight, but it increased their livers weight [P<0.001]. Histopathological evaluations showed .extensive liver damage. On the other hand, treatment with brittle star extract .ncreased liver weight, reduced. body weight and significantly altered other induced changes by carbon tetrachloride on liver structure such as hepatocytes number, Kupffer cells, and arteritis, which indicated the improvement of damaged liver tissue [P<0.001]
Conclusion: It was found that brittle star extract can exert protective effects on liver damages induced by carbon tetrachloride on male Wistar rat
ABSTRACT
Anti-cancer potential of marine natural products such as polysaccharides represented therapeutic potential in oncological researches. In this study, total polysaccharide from brittle star [Ophiocoma erinaceus [O. erinaceus]] was extracted and chemopreventive efficacy of Persian Gulf brittle star polysaccharide was investigated in HeLa human cervical cancer cells. To extract polysaccharide, dried brittle stars were ground and extracted mechanically. Then, detection of polysaccharide was performed by phenol sulfuric acid, Ultra Violet [UV]-sulfuric acid method and FTIR. The anti proliferative activity of isolated polysaccharide was examined by MTT assay and evaluation of cell death was done through morphological cell changes; Propodium Iodide staining, fluorescence microscopy and caspase-3, -9 enzymatic measurements. To assess its underlying mechanism, expression of Bax, Bcl-2 was evaluated. The polysaccharide detection methods demonstrated isolation of crude polysaccharide from Persian Gulf brittle star. The results revealed that O. erinaceus polysaccharide suppressed the proliferation of HeLa cells in a dose and time dependent manner. Morphological observation of DAPI and Acridine Orange/Propodium Iodide staining was documented by typical characteristics of apoptotic cell death. Flow cytometry analyses exhibited the accumulation of treated cells in sub-G1 region. Additionally, polysaccharide extracted induced intrinsic apoptosis via up-regulation of caspase-3, caspase-9 and Bax along with down-regulation of Bcl-2 in HeLa cells. Taken together, the apoptosis inducing effect of brittle star polysaccharide via intrinsic pathway confirmed the anti tumor potential of marine polysaccharide. Therefore, these findings proposed new insight into anti cancer properties of brittle star polysaccharide as a promising agent in cervical cancer treatment
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Mother-infant separation is one of the main causes of sleep-wake states disorders in neonatal intensive care unit [NICU]. The current study was conducted to investigate the effect of in-arms-holding by mothers on sleep-wake states disorders of preterm neonates. In a pilot study, through a semi-experimental pretest-posttest method, 35 preterm neonates with gestational age between 32 and 37 weeks and their mothers were selected from NICU of Valiasr Hospital, Tehran, Iran. Data collection process was carried out using the behavioral states scale of Newborn Individualized Developmental Care and Assessment Program. Sleep-wake states data were collected in three phases: 20 min before intervention, 70 min of intervention [mother holding], and 20 min after intervention. The collected data were analyzed using repeated measures analysis of variance [RM ANOVA] and Bonferroni test in the SPSS for Windows 17.0. About 57% of neonates were male. The results of RM ANOVA showed that there were significant differences between three phases of study in terms of deep sleep [P < 0.001, F = 20.400], light sleep [P < 0.001, F = 167.230], drowsiness [P < 0.001, F = 26.770], quietly awake [P < 0.001, F = 27.380] and crying [P = 0.001, F = 4.370], but there was no significant difference for actively awake. Holding the preterm neonates by their mothers seems to improve their sleep-wake states. Medical and nursing staff in NICUs and nurseries may be recommended to use this kind of care to prevent sleep and wake disorders of neonates
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The objective of this study is to determine risk factors causing increase in very low birth way [VLBW] neonatal mortality. The medical files of all neonates weighing <1500 gram, born in Vali-e-Asr hospital [2001-2004] were studied. Two groups of neonates [living and dead] were compared up to the time of hospital discharge or death. A total of 317 neonates were enrolled. A meaningful relationship existed between occurrence of death and low gestational age [P=0.02], low birth weight, lower than 1000 gram [P=0.001], Apgar score <6 at 5[th] minutes [P=0.001], resuscitation at birth [P=0.001], respiratory distress syndrome [P=0.001] need for mechanical ventilation [P=0.001], neurological complications [P=0.001] and intraventricular hemorrhage [P=0.001]. Regression analysis indicated that each 250 gram weight increase up to 1250 gram had protective effect, and reduced mortality rate. The causes of death of those neonates weighting over 1250 gram should be sought in factors other than weight. Survival rate was calculated to be 80.4% for neonates weighing more than 1000 gram. The most important high risk factors affecting mortality of neonates are: low birth weight, need for resuscitation at birth, need for ventilator use and intraventricular hemorrhage
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Ventilator Associated Pneumonia [VAP], developing in mechanically ventilated patients after 48 hours of mechanical ventilation, is the second most common nosocomial infection. Therefore, there is a vital need to study the etiology and risk factors associated with VAP in neonates. Neonates admitted to neonatal intensive care unit [NICU], over a period of one year and who required mechanical ventilation for more than 48 hours were enrolled consecutively into the study. Semi-quantitative assay of endotracheal aspirate was used for microbiological diagnoses of VAP.105CFU/ml was taken as the cut off between evidence of pathological infection and colonization. The primary outcome measure was the development of VAP. Secondary outcome measures were length of mechanical ventilation, NICU length of stay, hospital cost, and death. Thirty eight patients were enrolled [58% were boys and 42% were girls].42% of neonates developed VAP. The most common VAP organisms identified were Acinetobacter baumanni [43%]. On multiple regression analysis, duration of mechanical ventilation was associated with VAP [P=0.00]. Patients with VAP had greater need for mechanical ventilation [18.7 vs 6 median days], longer NICU length of stay [39 vs 21.5 median days] and higher total median hospital costs [79.5 vs 52 million rials] than those without VAP. The mortality rate was not different between two groups. In mechanically ventilated neonates, those with VAP had a prolonged need for mechanical ventilation, a longer NICU stay, and a higher hospital costs. Longer mechanical ventilation was associated with an increased risk of developing VAP in these patients. Developing of VAP didn't increase mortality in patients.
Subject(s)
Humans , Male , Female , Infant, Newborn , Intensive Care Units, Neonatal , Risk Factors , Patient Outcome Assessment , Infant, Newborn , Cross InfectionABSTRACT
Neonatal deaths stand for almost two-thirds of all deaths occurring in infants under one year of age. Congenital anomalies are responsible for 24.5% of these cases forming a highly important issue for health policy-makers. We studied the pre-, peri- and post-natal conditions of 77 patients with multiple congenital anomalies [MCA] through genetic counseling at Several university Hospitals, in Tehran, Iran. The collected data were subsequently analyzed using SPSS software. The patients did not have a good prognosis, demonstrating the need for the diagnosis of such diseases early in pregnancy to be of utmost importance. We screened for trisomy and nuchal translucency, which the first showed a low risk and the second showed normal results in most cases. Establishment of standards for prenatal diagnosis of congenital anomalies and monitoring their implementation seem to be necessary for the reduction of deaths due to congenital anomalies and infant mortality rate [IMR]
Subject(s)
Humans , Female , Male , Abnormalities, Multiple/diagnosis , Infant, Newborn , Perinatology , Infant Mortality , Nuchal Translucency Measurement , Prenatal Diagnosis , PregnancyABSTRACT
Evaluating the effect of vegetable oil, as a supplement to breast milk in increase the weight gaining of VLBW neonates. In this single blind; Randomized clinical trials, in NICU of Vali-asr Hospital, Tehran University of Medical Sciences, 2005-2006;A total of 48 VLBW neonates referred and admitted to NICU, who did not have any major GI [especially NEC], respiratory or cardiac diseases; participated randomly in two groups: intervention and control.Vegetable oil was added to the milk of 25 neonates [0.5 cc per 30cc of milk] and the other 25neonates with similar conditions that were selected as a control group, did not get any type of supplementary nutrition. Daily feeding volume in both groups was 150-200 cc for each kilogram of body weight. Weight gaining in interventional groups was considerably more than control group. [p<0.04].There were also significant statistical differences in hospitalization period between the two groups, 28.9 days in interventional and 20.33 days in control group, [p<0.03].However, no significant side effects were observed. There is no report regarding contraindication linking the use of vegetable oil intended for appropriate weight gaining or reducing hospitalization period to neonatal chronic diseases
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This study aims to describe the blood pressure profile of newborns of preeclampsia mothers in Vali-e-Asr hospital during 2003-2004. In this cross-sectional descriptive analytical study 200 mothers and their newborns were studied. Blood pressure of all newborns was checked by oscillometric method on the first day after birth and recorded in a questionnaire along with information pertaining to the mother, obtained by interview or through medical file retrieval. The newborns of mothers with high systolic [>140 mmHg] and diastolic [>90 mmHg] blood pressure had mean systolic [65.40 mmHg] and diastolic [42.85 mmHg] blood pressures higher than that in neonates of normotensive mothers[P <0.006]. Mean systolic and diastolic blood pressure of neonates whose mothers were preeclampsia [68.2/42.11 mmHg or chronically hypertensive [68.59/ 41.50 mmHg-] were significantly higher than neonates of normotensive mothers [P<0.0001 and P<0.002, respectively].Newborns of smokers had significantly higher blood pressures too [P<0.02]. Mother's blood pressure can affect neonatal blood pressure. Chronic hypertension, pre-eclampsia, and cigarette smoking in mothers can adversely alter neonatal blood pressure. These maternal conditions should be screened and managed as soon as possible
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Chylous ascites was diagnosed in a female neonate. Following the administration of a gastrografin enema, which showed the presence of gut malrotation, she was operated. This led to a complete recovery and optimal weight gain. For evaluation of chylous ascites in neonates, gut malrotation should be considered in order to prevent volvolus and further complications