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OBJECTIVE: This study evaluated the effects of a traditional Chinese medicine formula (TCMF) on muscle fiber characteristics in finishing pigs and the effects of the formula's extract (distilled water, ethyl acetate and petroleum ether extraction) on porcine cell proliferation and isoforms of myosin heavy chain (MyHC) gene expression in myocytes. METHODS: In a completely randomized design, ninety pigs were assigned to three diets with five replications per treatment and six pigs per pen. The diets included the basal diet (control group), TCMF1 (basal diet+2.5 g/kg TCMF) and TCMF2 (basal diet+5 g/kg TCMF). The psoas major muscle was obtained from pigs at the end of the experiment. Muscle fiber characteristics in the psoas major muscle were analyzed using myosin ATPase staining. Cell proliferation was measured using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) dye and cytometry. Isoforms of MyHC gene expression were detected by real-time quantitative polymerase chain reaction. RESULTS: The final body weight and carcass weight of finishing pigs were increased by TCMF1 (p<0.05), while the psoas major muscle cross-sectional area was increased by TCMF (p<0.05). The cross-sectional area and diameter of psoas major muscle fiber I, IIA, and IIB were increased by TCMF2 (p<0.05). The cross-sectional area and fiber diameter of psoas major muscle fiber IIA and IIB were increased by diet supplementation with TCMF1 (p<0.05). Psoas major muscle fiber IIA and IIB fiber density from the pigs fed the TCMF1 diet and the type IIB fiber density from the pigs fed the TCMF2 diet were lower compared to pigs fed the control diet (p<0.05). Pigs fed TCMF2 had a higher composition of type I fiber and a lower percentage of type IIB fiber in the psoas major muscle (p<0.05). The expression levels of MyHC I, MyHC IIa, and MyHC IIx mRNA increased and the amount of MyHC IIb mRNA decreased in the psoas major muscle from TCMF2, whereas MyHC I and MyHC IIx mRNA increased in the psoas major muscle from TCMF1 (p<0.05). Peroxisome proliferator-activated receptor γ coactivator-1α and CaN mRNA expression in the psoas major muscle were up-regulated by TCMF (p<0.05). Porcine skeletal muscle satellite cell proliferation was promoted by 4 µg/mL and 20 µg/mL TCMF water extraction (p<0.05). Both 1 µg/mL and 5 µg/mL of TCMF water extraction increased MyHC IIa, MyHC IIb, and MyHC IIx mRNA expression in porcine myocytes (p<0.05), while MyHC I mRNA expression in porcine myocytes was decreased by 5 µg/mL TCMF water extraction (p<0.05). Porcine myocyte MyHC I and MyHC IIx mRNA expression were increased, and MyHC IIa and MyHC IIb mRNA expression were down-regulated by 5 µg/mL TCMF ethyl acetate extraction (p<0.05). MyHC I and MyHC IIa mRNA expression in porcine myocytes were increased, and the MyHC IIb mRNA expression was decreased by 1 µg/mL TCMF ethyl acetate extraction (p<0.05). Four isoforms of MyHC mRNA expression in porcine myocytes were reduced by 5 µg/mL TCMF petroleum ether extraction (p<0.05). MyHC IIa mRNA expression in porcine myocytes increased and MyHC IIb mRNA expression decreased by 1 µg/mL in a TCMF petroleum ether extraction (p<0.05). CONCLUSION: These results indicated that TCMF amplified the psoas major muscle cross-sectional area through changing muscle fiber characteristics in finishing pigs. This effect was confirmed as TCMF extraction promoted porcine cell proliferation and affected isoforms of MyHC gene expression in myocytes.
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OBJECTIVE: This experiment investigated meat color, myoglobin content, enzyme activities, and expression of genes associated with oxidative potential of pigs slaughtered at different growth stages. METHODS: Sixty 4-week-old Duroc×Landrace×Yorkshire pigs were assigned to 6 replicate groups, each containing 10 pigs. One pig from each group was sacrificed at day 35, 63, 98, and 161 to isolate longissimus dorsi and triceps muscles. RESULTS: Meat color scores were higher in pigs at 35 d than those at 63 d and 98 d (p<0.05), and those at 98 d were lower than those at 161 d (p<0.05). The total myoglobin was higher on 161 d compared with those at 63 d and 98 d (p<0.05). Increase in the proportions of metmyoglobin and deoxymyoglobin and a decrease in oxymyoglobin were observed between days 35 and 161 (p<0.05). Meat color scores were correlated to the proportion of oxymyoglobin (r = 0.59, p<0.01), and negatively correlated with deoxymyoglobin and metmyoglobin content (r = -0.48 and -0.62, p<0.05). Malate dehydrogenase (MDH) activity at 35 d and 98 d was higher than that at 161 d (p<0.05). The highest lactate dehydrogenase/MDH ratio was achieved at 161 d (p<0.05). Calcineurin mRNA expression decreased at 35 d compared to that at 63 d and 98 d (p<0.05). Myocyte enhancer factor 2 mRNA results indicated a higher expression at 161 d than that at 63 d and 98 d (p<0.05). CONCLUSION: Porcine meat color, myoglobin content, enzyme activities, and genes associated with oxidative potential varied at different stages.
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OBJECTIVE: To observe the variability of hemoglobin (HB) level in patients with renal anemia, and to analyze its relationship with effect of repeated blood transfusion therapeutic in patients. METHODS: A retrospective cohort study and propensity score matching method were used, 60 patients with renal anemia who had effective treatment with repeated blood transfusion in Changzhou No.2 People's Hospital from May 2018 to May 2021 were retrospectively analyzed and set as the effective group; 153 patients with renal anemia who had ineffective treatment with repeated blood transfusion in the hospital in the same period were collected and set as the ineffective group, the propensity score matching method was used, the patients who were effective and ineffective in repeated blood transfusion were matched 1â¶1 for analysis; the medical records and laboratory indexes of the two groups were checked; the Hb level of patients within 6 months (1/month) were recorded, the residual standard deviation (Res-SD) of Hb of patients was calculated according to the Hb level and evaluated the variability of Hb level; the relationship between HB variability level and therapeutic effect of repeated blood transfusion in patients with renal anemia was analyzed. RESULTS: After propensity score matching, there was no statistical significant difference between the two groups in terms of baseline data such as age, sex, dialysis age and BMI (P>0.05). The levels of serum albumin and transferrin of patients in the ineffective group were significantly lower than those of patients in the effective group (P<0.05); at 1 and 2 months of the observation period, there was no statistical significant difference in Hb levels of patients in both groups (P>0.05); the Hb level of patients in the ineffective group was significantly lower than that of patients in the effective group at 3, 5 and 6 months, and significantly higher than that of patients in the effective group at 4 months (P<0.05); the Res-SD of male patients and female patients in the ineffective group were respectively significantly higher than that of male patients and female patients in the effective group (P<0.05). Logistic regression analysis results showed that high variability of Hb level (Res-SD) was a risk factor for the ineffective treatment of repeated blood transfusion in patients with renal anemia (OR>1, P<0.05); the decision curve results showed that, when the high-risk threshold was 0.0-1.0, Res-SD predicted the net benefit rates of male and female patients with renal anemia were greater than 0, which was clinically significant, the smaller the high-risk threshold in the above range, the greater the net benefit rate. CONCLUSION: The therapeutic effect of repeated blood transfusion in patients with renal anemia may be related to the variability of Hb level.
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Anemia , Enfermedades Renales , Humanos , Masculino , Femenino , Estudios Retrospectivos , Hemoglobinas/uso terapéutico , Anemia/terapia , Enfermedad Crónica , Transfusión SanguíneaRESUMEN
OBJECTIVE: To investigate the effects of Zhi Zi (Fructus Gardeniae) on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet in the rat. METHODS: A rat model of NAFLD was established using a high-fat diet. Twenty one rats were randomly divided into a normal group, a model group and a Zhi Zi treatment group, 7 rats per group. Drinking water and the drug were intragastrically administrated for 5 weeks. Samples were then taken to observe pathological changes of the liver tissue (HE staining); changes in the fat metabolism pathway e. g. triglyceride (TG) and free fatty acid (FFA) content; alterations in liver function, i.e. serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity; and differences in tumor necrosis factor alpha (TNF-alpha) and P-IkB protein expression in the liver tissue. RESULTS: Fatty degeneration and vacuole-like changes of different degrees occurred in hepatic cells of the model group. Markers for fat metabolism, serum ALT and AST activities, and expression of TNF-alpha and P-IkB proteins in liver tissue significantly increased. Fat metabolism in the Zhi Zi group significantly reduced, as shown by a drop in marker levels. Serum ALT and AST activities, and expression of TNF-alpha, P-IkB proteins in liver tissue were also significantly decreased in this group. CONCLUSION: Zhi Zi has a very strong inhibitory action on lipidosis and inflammatory injury in the rat model of NAFLD. This mechanism may possibly be related to the inhibition of the free fatty acid metabolism pathway.
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Medicamentos Herbarios Chinos/administración & dosificación , Hígado Graso/tratamiento farmacológico , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Modelos Animales de Enfermedad , Hígado Graso/sangre , Hígado Graso/genética , Hígado Graso/metabolismo , Expresión Génica/efectos de los fármacos , Humanos , Proteínas I-kappa B/genética , Proteínas I-kappa B/metabolismo , Masculino , Enfermedad del Hígado Graso no Alcohólico , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Background: Nanoparticle albumin-bound paclitaxel (nab-PTX) has exhibited clinical efficacy in breast cancer treatment, but toxicities can be yielded more at the same time. We did this meta-analysis aiming to unambiguously compare nab-PTX with conventional solvent-based paclitaxel (sb-PTX) in breast cancer patients of all stages. Method: Pubmed, Embase and Cochrane Library were searched for head-to-head randomized controlled trials of nab-PTX and sb-PTX in breast cancer. Risk ratio (RR) with 95% confidence interval was used for dichotomous variables while Hazard ratio (HR) was used for time-to-event outcomes. Results: Our review finally included 9 studies with 3508 patients. Nab-PTX showed a benefit on objective response rate (ORR) (RR=1.22 [1.04-1.43], P=0.01) as well as non-inferiority compared with sb-PTX in disease control rate (DCR) (RR=1.01 [0.98-1.04], P=0.44), overall survival (OS) (HR=0.99 [0.93-1.05], P=0.81) and disease free survival/progression free survival (DFS/PFS) (HR=0.92 [0.81-1.05], P=0.21). However, when it comes to toxicities (fatigue, nausea or vomiting, peripheral sensory neuropathy and adverse event related discontinuation), results favored sb-PTX (RR=2.89 [1.07-7.8], 3.15 [1.78-5.59], 2.11 [1.32-3.37], 2.02 [1.61-2.53]; P<0.05). Patients with metastatic tumors or undergoing conventional schedule responses better to nab-PTX than the compared groups (RR of ORR in metastatic vs early or locally advanced patients: 1.46 [1.09-1.96] vs 1.01 [0.94-1.08]; conventional vs dose dense group: 1.59 [1.23-2.06] vs 1.01 [0.91-1.12]). Conclusions: Nab-PTX can improve ORR compared with paclitaxel and should be given priority to when aiming to reduce tumor load in breast cancer. Sb-PTX of dose dense schedule is recommended when toxicity of nab-PTX is hard to bear for breast cancer patients.
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A heterologous direct competitive enzyme-linked immunosorbent assay (ELISA) for parathion residue determination is described based on a monoclonal antibody and a new competitor. The effects of several physicochemical factors, such as methanol concentration, ionic strength, pH value, and sample matrix, on the performance of the ELISA were optimized for the sake of obtaining a satisfactory assay sensitivity. Results showed that when the assay medium was in the optimized condition (phosphate buffer solution [PBS] containing 10% [v/v] methanol and 0.2 mol/L NaCl at a pH value of 5.0), the sensitivity (estimated as the IC(50) value) and the limit of detection (LOD, estimated as the IC(10) value) were 1.19 and 0.08 ng/ml, respectively. The precision investigation indicated that the intraassay precision values all were below 10% and that the interassay precision values ranged from 4.89 to 19.12%. In addition, the developed ELISA showed a good linear correlation (r(2)=0.9962) to gas chromatography within the analyte's concentration range of 0.1 to 16 ng/ml. When applied to the fortified samples (parathion adding level: 5-15 microg/kg), the developed ELISA presented mean recoveries of 127.46, 122.52, 91.92, 124.01, 129.72, 99.37, and 87.17% for tomato, cucumber, banana, apple, orange, pear, and sugarcane, respectively. Results indicated that the established ELISA is a potential tool for parathion residue determination.
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Ensayo de Inmunoadsorción Enzimática/métodos , Análisis de los Alimentos/métodos , Insecticidas/análisis , Paratión/análisis , Ensayo de Inmunoadsorción Enzimática/instrumentación , Análisis de los Alimentos/instrumentación , Frutas/química , Concentración de Iones de Hidrógeno , Insecticidas/química , Metanol , Estructura Molecular , Concentración Osmolar , Paratión/química , Verduras/químicaRESUMEN
Professor HUANG Lin-na's experience in treatment of Tourette syndrome with Fang's scalp acupuncture were introduced. Professor HUANG believes that this disease is in category of tremor in TCM. Pathogenic wind is the key in its pathogenesis and liver, spleen and kidney are closely related. Hence, the treatment focuses on eliminating pathogenic wind and regulating the function of liver, spleen and kidney. The cerebrum is the regulation center in human body. The abnormal somatic function can be adjusted by acupuncture at the scalp area where the cerebral cortical function is projected. Fang's scalp acupuncture is suitable in treatment of Tourette syndrome. Such scalp acupuncture was introduced in this paper with the typical case reported so as to provide a new approach to clinical treatment.
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Terapia por Acupuntura , Síndrome de Tourette , Humanos , Cuero Cabelludo , Bazo , Síndrome de Tourette/terapiaRESUMEN
PURPOSE: To investigate the effect of adrenomedullin on the cell numbers and apoptosis of endothelial progenitor cells (EPCs). METHODS: Mononuclear cells were isolated from peripheral blood by Ficoll density gradient centrifugation. The cells were stimulated with adrenomedullin, before and after the treatment of adrenomedullin-receptor antagonist, adrenomedullin 22-52, or a PI3K inhibitor LY294002. RESULTS: Adrenomedullin dose-dependently increased the number of EPCs (P < 0.05). Adrenomedullin also significantly decreased apoptosis rate of EPCs in a concentration-dependent manner (P < 0.05). In the isolated human mononuclear cells pretreated with adrenomedullin 22-52 or LY294002, adrenomedullin failed to increase the number of EPCs or to reduce the level of apoptosis. CONCLUSIONS: Adrenomedullin increases the number of EPCs and decreases their apoptosis. These actions are likely mediated by PI3K signaling pathways. The clinical importance of these favourable effects on EPCs remains to be determined.
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Adrenomedulina/farmacología , Apoptosis/efectos de los fármacos , División Celular/efectos de los fármacos , Endotelio Vascular/citología , Endotelio Vascular/fisiología , Células Madre/citología , Células Madre/fisiología , Cromonas/farmacología , Endotelio Vascular/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Humanos , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/fisiología , Morfolinas/farmacología , Células Madre/efectos de los fármacosRESUMEN
BACKGROUND: Cancer patients undergoing surgical procedure often suffer from bowel dysfunction and postoperative ileus (POI). Cancer management for early recovery of bowel function is still a challenging topic. Acupuncture has been commonly used in a variety of gastrointestinal diseases. The aim of this study is to evaluate the effects of acupuncture therapy to reduce the duration of POI and enhance bowel function in cancer patients. METHODS: We will systematically screen all randomized controlled trials (RCTs) published through electronically and hand searching. The following search engines including Medline, EMBASE, Cochrane CENTRAL, the Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, VIP Information, Wanfang Data, one Japanese database (Japan Science and Technology Information Aggregator, Electronic) and 2 Korean Medical Databases (Korean Studies Information, and Data Base Periodical Information Academic) will be retrieved. Supplementary sources will be searched including gray literature, conference proceedings, and potential identified publications. Two reviewers will independently conduct the trial inclusion, data extraction and assess the quality of studies. The time to first passing flatus and time to first bowel motion will be assessed as the primary outcomes. Adverse effects, time to first bowel sound, visual analog scale (VAS) pain score, hospital stay, and postoperative analgesic requirement will be measured as secondary outcomes. Methodological quality will be evaluated according to the Cochrane risk of bias. Details of interventions will be assessed by the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) checklist. All analyses will be applied by RevMan (version 5.3) and StataSE (version 12). ETHICS AND DISSEMINATION: This systematic review will provide up-to-date information on acupuncture therapy for early recovery of bowel function in cancer patients. This review does not require ethical approval and will be reported in a peer-reviewed journal and presented at a relevant conference. TRIAL REGISTRATION NUMBER: PROSPERO CRD42016049633.
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Terapia por Acupuntura , Ileus/etiología , Ileus/terapia , Neoplasias/cirugía , Complicaciones Posoperatorias/terapia , Humanos , Neoplasias/complicaciones , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Revisiones Sistemáticas como AsuntoRESUMEN
BACKGROUND: MEK inhibitors are a group of drugs that have shown reliable effects in the treatment of metastatic melanoma and non-small-cell lung cancer. Peripheral edema is an adverse event associated with MEK inhibitors; however, there has been no systematic attempt to evaluate peripheral edema data observed with these agents. This meta-analysis aimed to determine the risk of peripheral edema in cancer patients treated with MEK inhibitors. MATERIALS AND METHODS: The authors searched PubMed, the Cochrane Library, EMBASE, and Clinical Trials.gov without language restriction. The final search was conducted on January 9, 2017. Risk ratios (RR) with 95% confidence intervals (CI) were calculated for dichotomous data. Heterogeneity was calculated and reported via Tau2, Chi2, and I2 analyses. RESULTS: A total of 13 eligible studies were obtained. Patients treated with MEK inhibitors (Trametinib and Selumetinib) had an increased risk overall of peripheral edema (RR = 3.05, 95% CI = 1.98-4.70; p < .00001), but the MEK inhibitors (Trametinib and Selumetinib) did not increase the risk of high grade edema (RR = 1.88, 95% CI = 0.66-5.35; p = .24). Sub-group analysis, based on cancer type (melanoma vs non-melanoma), found that the peripheral edema risk in melanoma patients is higher than that in non-melanoma patients (p = .03). However, no significant difference was observed in terms of high-grade edema and other sub-groups (trametinib vs selumetinib; monotherapy vs combination). Due to the absence of cobimetinib data, the result about cobimetinib was not involved. CONCLUSION: This meta-analysis reveals that the use of MEK inhibitors is associated with an increased risk of peripheral edema in cancer patients. Oncologists should be aware of the risk and perform regular assessments.
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Edema/inducido químicamente , Neoplasias/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Humanos , Oportunidad Relativa , Inhibidores de Proteínas Quinasas/efectos adversos , RiesgoRESUMEN
OBJECTIVES: The aim of this study was to evaluate the effects of acupuncture therapy to reduce the duration of postoperative ileus (POI) and to enhance bowel function in cancer patients. METHODS: A systematic search of electronic databases for studies published from inception until January 2017 was carried out from six databases. Randomized controlled trials (RCTs) involving the use of acupuncture and acupressure for POI and bowel function in cancer patients were identified. Outcomes were extracted from each study and pooled to determine the risk ratio and standardized mean difference. RESULTS: 10 RCTs involving 776 cancer patients were included. Compared with control groups (no acupuncture, sham acupuncture, and other active therapies), acupuncture was associated with shorter time to first flatus and time to first defecation. A subgroup analysis revealed that manual acupuncture was more effective on the time to first flatus and the time to first defecation; electroacupuncture was better in reducing the length of hospital stay. Compared with control groups (sham or no acupressure), acupressure was associated with shorter time to first flatus. However, GRADE approach indicated a low quality of evidence. CONCLUSIONS: Acupuncture and acupressure showed large effect size with significantly poor or inferior quality of included trials for enhancing bowel function in cancer patients after surgery. Further well-powered evidence is needed.
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INTRODUCTION: This systematic review protocol aims to provide the methods used to evaluate the effectiveness and safety of acupuncture therapy for treating vascular dementia. METHODS AND ANALYSIS: The following eight databases will be searched from inception to July 2017: Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, EMBASE, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Database and Wanfang Database. All randomised controlled trials in English or Chinese related to acupuncture for vascular dementia will be included. Outcomes will include change in cognitive function and activities of daily living. The incidence of adverse events will be assessed for safety evaluation. Study inclusion, data extraction and quality assessment will be performed independently by two reviewers. Assessment of risk of bias and data synthesis will be performed using Review Manager software. ETHICS AND DISSEMINATION: Ethics approval is not required because individual patient data are not included. The findings of this systematic review will be disseminated through peer-reviewed publication or conference presentations. PROSPERO REGISTRATION NUMBER: CRD42017071820.
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Terapia por Acupuntura , Demencia Vascular/terapia , Terapia por Acupuntura/efectos adversos , Terapia por Acupuntura/métodos , Humanos , Evaluación de Resultado en la Atención de Salud/métodos , Proyectos de Investigación , Revisiones Sistemáticas como AsuntoRESUMEN
This study was designed to investigate the function of 17ß-estradiol (17ß-E2) against oxidative stress on the cell death of mice bone marrow mesenchymal stem cells (BMSCs) induced by hydrogen peroxide (H2O2). BMSCs were treated with 17ß-E2 for 24h and then treated with 100µM H2O2 for 1h. Cell viability, apoptosis, caspase-9 mRNA, JNKs (Jun N-terminal kinases) and c-Jun protein expression in BMSCs were evaluated. Cell apoptosis of BMSCs were increased in a dose-dependent manner after treated with H2O2 compared to control group. But pretreatment with 17ß-E2 can inhibit apoptosis of BMSCs, preserve the mitochondrial transmembrane potential, decrease caspase-9 mRNA, JNK1/2 and c-Jun protein expression. In conclusion, 17ß-E2 exerts antiapoptotic effects in BMSCs which related to the mitochondria death pathway and JNKs pathway. The study revealed that 17ß-E2 can reduce the donor stem cells damage.
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Apoptosis/efectos de los fármacos , Estradiol/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Caspasa 9/metabolismo , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Estradiol/administración & dosificación , Estrógenos/administración & dosificación , Estrógenos/farmacología , Peróxido de Hidrógeno/toxicidad , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Células Madre Mesenquimatosas/metabolismo , RatonesRESUMEN
A novel procedure for parathion hapten design is described. The optimal antigen for parathion was selected after molecular modeling studies of six types of potentially immunizing haptens with the aim to identify the best mimicking target analyte. Heterologous competitive indirect enzyme-linked immunosorbent assay (ELISA) was developed after screening a battery of competitors as coating antigens. The relationship between the heterology degree of the competitor and the resulting immunoassay detectability was investigated according to the electronic similarities of the competitor haptens and the target analyte. Molecular modeling and principal component analysis were performed to understand the electronic distribution and steric parameters of the haptens at their minimum energetic levels. The results suggested that the competitors should have a high heterology to produce assays with good detectability values. An indirect competitive ELISA was finally selected for further investigation. The immunoassay had an IC50 value of 4.79 ng mL(-1) and a limit of detection of 0.31 ng mL(-1). There was little or no cross-reactivity to similar compounds tested except for the insecticide parathion-methyl, which showed a cross-reactivity of 7.8%.