Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 17 de 17
Filter
Add more filters










Publication year range
2.
J Clin Med Res ; 16(2-3): 75-80, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38550545

ABSTRACT

Background: Genetic polymorphisms of platelet glycoprotein IIIa (GPIIIa gene) have been investigated intensively in several thrombotic diseases, but their role in cardiovascular diseases remains controversial. This study aimed to investigate the association between platelet glycoprotein IIIa PlA1/PlA2 polymorphism and susceptibility to myocardial infarction in non-diabetics. Methods: A total of 200 participants were recruited for the study, 100 non-diabetic patients with myocardial infarction and 100 apparently healthy volunteers as a control group. GPIIIa PlA1/PlA2 polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism. Results: The distribution of GPIIIa PlA1/PlA2 polymorphic genotypes among the study groups was significantly different (P value = 0.00). The PlA1/PlA2 and PlA2/PlA2 genotypes were more frequent in the patients with myocardial infarction while the genotype PlA1/PlA1 was more prevalent in the control group. There was a statistically significant association between the PlA1/PlA1 genotype and reduced risk of both ST-segment elevation myocardial infarction (odds ratio (OR) = 0.19; 95% confidence interval (CI): 0.09 - 0.34, P value = 0.00) and non-ST-segment elevation myocardial infarction (OR = 0.21; 95% CI: 0.09 - 0.45, P value = 0.00). The genotype PlA1/PlA2 was found to be associated with an increased risk of both types of myocardial infarction (OR = 6.0; 95% CI: 2.61 - 13.8, P value = 0.00 for ST-segment elevation myocardial infarction and OR = 6.65; 95% CI: 2.69 - 16.45, P value = 0.00 for non- ST-segment elevation myocardial infarction. In the patients carrying the PlA1/PlA2 genotype, the risk of ST-segment elevation myocardial infarction was increased to about 14 folds in the presence of family history (OR: 13.57, 95% CI: 1.42 - 130.03, P value = 0.02), and the risk of non-ST-segment elevation myocardial infarction increased to about 18 folds in the smokers carrying the genotype PlA2/PlA2 (OR: 17.63, 95% CI: 0.96 - 324.70, P value = 0.05). Conclusions: The GPIII PlA1/PlA1 genotype is associated with a reduced risk of ST-segment elevation and non-ST-segment elevation myocardial infarction, while PlA1/PlA2 is associated with an increased risk of both types of myocardial infarction.

3.
J Anim Physiol Anim Nutr (Berl) ; 108(4): 883-890, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38353323

ABSTRACT

This study investigated the effects of in-ovo inoculation of betaine on hatchability, hatching weight, and intestinal development, as well as serum and expression levels of some antioxidants in the posthatched chicks. A total of 350 fertile eggs of Hubbard efficiency plus breeder's flock were incubated at normal incubation temperature (37.5°C) and randomly assembled into 3 groups with 4 replicates, and 25 eggs per each. The experimental groups were allocated as noninjected control group (CN), diluent-injected group (CP, 0.1 mL saline), and betaine-injected group (B, 2.5 mg in 0.1 mL saline). The injections were performed in the air cells of the eggs on the 12th day of the embryonic phase. Hatchability percentage, hatching weight, serum-reduced glutathione (GSH), and superoxide dismutase (SOD) were estimated in 7-day-old chicks. Moreover, expression levels of the nuclear factor erythroid 2-related factor 2 (Nrf2) and SOD were determined in the breast skeletal muscles of chicks. Jejunum histo-morphometric analysis was assessed with computerised morphometric measurements. The results revealed that the hatchability percentage was not influenced by in-ovo injection of betaine or vehicle while betaine significantly increased the hatchling's weight of chicks. Moreover, there were a significant increase in SOD and Nrf2 mRNA expression levels. In-ovo injection of betaine significantly induced positive effects on intestinal morphometry by ameliorating the jejunal villus length, the ratio of villus height to villus width, and absorptive surface area.


Subject(s)
Antioxidants , Betaine , Chickens , Intestines , Animals , Betaine/pharmacology , Betaine/administration & dosage , Chickens/physiology , Chickens/blood , Antioxidants/metabolism , Antioxidants/pharmacology , Intestines/drug effects , Intestines/physiology , Ovum/drug effects , Gene Expression Regulation, Developmental/drug effects , Muscle, Skeletal/drug effects , Gene Expression Regulation/drug effects , Chick Embryo/drug effects
4.
BMC Bioinformatics ; 25(1): 17, 2024 Jan 11.
Article in English | MEDLINE | ID: mdl-38212692

ABSTRACT

BACKGROUND: qPCR is a widely used technique in scientific research as a basic tool in gene expression analysis. Classically, the quantitative endpoint of qPCR is the threshold cycle (CT) that ignores differences in amplification efficiency among many other drawbacks. While other methods have been developed to analyze qPCR results, none has statistically proven to perform better than the CT method. Therefore, we aimed to develop a new qPCR analysis method that overcomes the limitations of the CT method. Our f0% [eff naught percent] method depends on a modified flexible sigmoid function to fit the amplification curve with a linear part to subtract the background noise. Then, the initial fluorescence is estimated and reported as a percentage of the predicted maximum fluorescence (f0%). RESULTS: The performance of the new f0% method was compared against the CT method along with another two outstanding methods-LinRegPCR and Cy0. The comparison regarded absolute and relative quantifications and used 20 dilution curves obtained from 7 different datasets that utilize different DNA-binding dyes. In the case of absolute quantification, f0% reduced CV%, variance, and absolute relative error by 1.66, 2.78, and 1.8 folds relative to CT; and by 1.65, 2.61, and 1.71 folds relative to LinRegPCR, respectively. While, regarding relative quantification, f0% reduced CV% by 1.76, 1.55, and 1.25 folds and variance by 3.13, 2.31, and 1.57 folds regarding CT, LinRegPCR, and Cy0, respectively. Finally, f0% reduced the absolute relative error caused by LinRegPCR by 1.83 folds. CONCLUSIONS: We recommend using the f0% method to analyze and report qPCR results based on its reported advantages. Finally, to simplify the usage of the f0% method, it was implemented in a macro-enabled Excel file with a user manual located on https://github.com/Mahmoud0Gamal/F0-perc/releases .

5.
Animals (Basel) ; 13(6)2023 Mar 11.
Article in English | MEDLINE | ID: mdl-36978571

ABSTRACT

Inclusion of microbial fermented soybean meal in broiler feed has induced advantageous outcomes for their performance and gastrointestinal health via exhibiting probiotic effects. In this study, soybean meal (SBM) was subjected to double-stage microbial fermentation utilizing functional metabolites of fungi and bacteria. In broiler diet, DFSBM replaced SBM by 0, 25, 50 and 100%. DFSBM was reported to have higher protein content and total essential, nonessential and free amino acids (increased by 3.67%, 12.81%, 10.10% and 5.88-fold, respectively, compared to SBM). Notably, phytase activity and lactic acid bacteria increased, while fiber, lipid and trypsin inhibitor contents were decreased by 14.05%, 38.24% and 72.80%, respectively, in a diet containing 100% DFSBM, compared to SBM. Improved growth performance and apparent nutrient digestibility, including phosphorus and calcium, and pancreatic digestive enzyme activities were observed in groups fed higher DFSBM levels. In addition, higher inclusion levels of DFSBM increased blood immune response (IgG, IgM, nitric oxide and lysozyme levels) and liver antioxidant status. Jejunal amino acids- and peptide transporter-encoding genes (LAT1, CAT-1, CAT-2, PepT-1 and PepT-2) were upregulated with increasing levels of DFSBM in the ration. Breast muscle crude protein, calcium and phosphorus retention were increased, especially at higher inclusion levels of DFSBM. Coliform bacteria load was significantly reduced, while lactic acid bacteria count in broiler intestines was increased with higher dietary levels of DFSBM. In conclusion, replacement of SBM with DFSBM positively impacted broiler chicken feed utilization and boosted chickens' amino acid transportation, in addition to improving the nutritional value of their breast meat.

6.
Brain Sci ; 12(4)2022 Apr 16.
Article in English | MEDLINE | ID: mdl-35448038

ABSTRACT

The outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signifies a serious worldwide concern to public health. Both transcriptome and proteome of SARS-CoV-2-infected cells synergize the progression of infection in host, which may exacerbate symptoms and/or progression of other chronic diseases such as Parkinson's disease (PD). Oxidative stress is a well-known cause of endoplasmic reticulum (ER) stress observed in both SARS-CoV-2 and PD. In the current study, we aimed to explore the influence of PKR-like ER kinase (PERK) stress pathway under SARS-CoV-2-mediated infection and in human cell model of PD. Furthermore, we investigated whether they are interconnected and if the ER stress inhibitors could inhibit cell death and provide cellular protection. To achieve this aim, we have incorporated in silico analysis obtained from gene set enrichment analysis (GSEA), a literature review and laboratory data. The neurotoxin, 6-hydroxy dopamine (6OHDA), was used to mimic the biochemical and neuropathological characteristics of PD by inducing oxidative stress in dopamine-containing neurons differentiated from ReNVM cell line (dDCNs). Furthermore, we explored if ER stress influences activation of caspases-2, -4 and -8 in SARS-CoV-2 and in stressed dDCNs. Our laboratory data using Western blot, immunocytochemistry and 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) analyses indicated that 6OHDA-induced toxicity triggered activation of caspases-2, -4 and -8 in dDCNs. Under SARS-CoV-2 infection of different cell types, GSEA revealed cell-specific sensitivities to oxidative and ER stresses. Cardiomyocytes and type II alveolar epithelial-like cells were more vulnerable to oxidative stress than neural cells. On the other side, only cardiomyocytes activated the unfolded protein response, however, the PERK pathway was operative in both cardiomyocytes and neural cells. In addition, caspase-4 activation by a SARS-CoV-2 was observed via in silico analyses. These results demonstrate that the ER stress pathway under oxidative stress in SARS-CoV-2 and PD are interconnected using diverse pathways. Furthermore, our results using the ER stress inhibitor and caspase specific inhibitors provided cellular protection suggesting that the use of specific inhibitors can provide effective therapeutic approaches for the treatment of COVID-19 and PD.

7.
Res Social Adm Pharm ; 18(9): 3580-3587, 2022 09.
Article in English | MEDLINE | ID: mdl-35361567

ABSTRACT

BACKGROUND: Inadequate numeracy is a barrier to patients' understanding of their health. No measure of numeracy related to antibiotic use is available. OBJECTIVE: to develop and validate a measure of numeracy of antibiotic use, and to make this measure available in the Arabic language and context. METHODS: Best practices for developing, translating and validating scales were consulted to develop an anonymous survey administered on SurveyMonkey. Ten open-ended questions for which participants provided an answer assessed basic numeracy covering fractions, percentages, proportionality, measurement, and estimation, contextualized to real life situations. A panel of five experts, and 10 cognitive debriefings provided face and content validity for the tool. Individuals ≥18 years, who had mastery of Arabic or English were included. Exploratory factor analysis was performed to characterize the psychometric properties of the items, using principal-component analysis. Convergent validity was established by comparing numeracy scores with the antibiotic knowledge scale scores. Differences in numeracy scores according to sociodemographic variables were tested using multivariate analyses of variance. RESULTS: Two hundred fifty-four responses were obtained, giving a response rate of 63.5%. A two-factor structure which explained 44.2% of the variance evolved: "Mathematical knowledge and problem-solving skills" and "Numeracy-related practices and experience". An acceptable reliability of Cronbach's alpha coefficient = 0.713. Higher numeracy scores were significantly correlated with the scores of the antibiotic knowledge (r = 0.205, p < 0.01) and factor one within the tool: "side effects and resistance" (r = 0.162, p = 0.05). Participants with University/College education presented higher levels of numeracy-related practices and experience than those with high-school education. Likewise, participants with medical insurance presented with higher numeracy scores than those without. CONCLUSIONS: A valid and reliable measure of antibiotic numeracy in English and Arabic was created. The tool could identify patients with low numeracy who are candidates for targeted interventions and intensive education on appropriate antibiotic use.


Subject(s)
Anti-Bacterial Agents , Health Literacy , Anti-Bacterial Agents/therapeutic use , Humans , Psychometrics , Reproducibility of Results , Surveys and Questionnaires , Translating
8.
Anim Reprod ; 18(4): e20210104, 2021.
Article in English | MEDLINE | ID: mdl-34904018

ABSTRACT

Thirty healthy Sohagi ram lambs with an average age of 188.6±7.3 days were used to study the effect of pre-pubertal growth rate on some physiological parameters and sexual behavioral patterns at puberty. Ram lambs were divided into three groups (10 animals per each group) according to the previous growth rate until 6 months of age. Groups were marked as fast, medium and slow growing. Animal groups were housed in closed barns with access to an open area. Results showed that age and weight of ram lambs at puberty were significantly affected (P<0.05) by the pre-pubertal growth rate. Ram lambs in the fast growing group were reached to onset puberty firstly at 272.6 days with body weight (BW) 37.1 kg on average then ram lambs in medium group (284.8 days with BW 32.7 kg), while ram lambs in slow growing group were the last (314.1 days with BW 32.5 kg). Blood testosterone concentration at puberty was not significantly different among growing groups (1.494± 0.03 ng/ml on average, ranged from 1.287 to 1.902 ng/ml). Testes measurements from 6 months of age until puberty show that ram lambs in fast growing group had the highest values of testes length, circumference and volume followed by those in medium and slow growing group. Sexual behavioral observation showed that flehmen and mounting behavior were significantly higher for ram lambs in fast growing group (5.63 and 6.75 number/12h) than slow growing group (4.25 and 5.38 number/12h) while in medium growing group were intermediate (4.88 and 5.88 number/12h). From these findings, could be concluded that age, weight and sexual behavioral patterns of Sohagi ram lambs at puberty were affected by pre-pubertal growth rate, and the breeders should strive to achieve good growth rates for their lambs before puberty which led to improving reproductive performance.

9.
J Infect Dev Ctries ; 14(12): 1352-1360, 2020 12 31.
Article in English | MEDLINE | ID: mdl-33378275

ABSTRACT

INTRODUCTION: The recently discovered novel coronavirus disease (COVID-19) has emerged in Wuhan, China, since January 2020. Egypt reported a low incidence of infection when compared with other countries. The aim of the study was to assess the characterization of COVID-19 infection among the Egyptian population. METHODOLOGY: Data were collected from a single COVID-19 quarantine hospital in Cairo. A total number of 195 cases were included with their clinical, laboratory, and radiological data. RESULTS: Three different age groups behaved differently for COVD-19 infection. The pediatric age group was asymptomatic entirely, the middle age group (18-50 years) were asymptomatic in 53.3% of cases, while 77.9% of those above 50 years were symptomatic (p ≤ 0.001). The latter group had a high incidence of COVID-pneumonia in (83.1%), and moderate to critical presentations were encountered in 66.3% of them. Neutrophil to lymphocyte (N/L) ratio correlated directly with the age and case severity. C-reactive protein (CRP) and computed tomography scan chest (CT-chest) had added value on COVID-19 diagnosis in suspected cases. CONCLUSIONS: In Egypt, patients above 50 years are at a higher risk for symptomatic COVID-19 infection and leaner for moderate to critical COVID-19 presentation. The triad of CT-chest, CRP, and N/L ratio could be an integrated panel for assessing disease severity.


Subject(s)
Asymptomatic Infections/epidemiology , COVID-19/diagnostic imaging , COVID-19/physiopathology , Hospitalization , Adolescent , Adult , Age Factors , COVID-19/epidemiology , Child , Egypt/epidemiology , Female , Humans , Lymphocytes/cytology , Male , Middle Aged , Neutrophils/cytology , Retrospective Studies , Risk Factors , Severity of Illness Index , Tomography, X-Ray Computed , Young Adult
10.
J Nanobiotechnology ; 17(1): 98, 2019 Sep 17.
Article in English | MEDLINE | ID: mdl-31530277

ABSTRACT

The authors apologized for the unfortunate error in figure during publication of the article and they also explained that some of the solid grey graphs in Fig. 5 are intentionally based on the same data. For 8 different surface makers (CD14, CD73, CD34, CD105, CD19, CD90, CD45, HA-DR) in accordance to the guidelines of the manufacturer a panel of 4 different isotype controls were used, corresponding to 4 different fluorescence channels.

11.
Ophthalmic Res ; 62(3): 150-156, 2019.
Article in English | MEDLINE | ID: mdl-31167213

ABSTRACT

PURPOSE: To study the astigmatic correction of high post-keratoplasty astigmatism using Femtosecond laser (FSL)-assisted Arcuate Keratotomy (FS-AK). METHODS: A prospective interventional cohort study. We enrolled 17 eyes with high degree of irregular astigmatism, scheduled for FS-AK. FSL was used to perform paired arcuate incisions 1.00 mm inside the graft. Patients' uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), and astigmatic change were recorded and followed up to 1 year after surgery. Vector analysis using Alpins' method was done to analyze the astigmatic correction. RESULTS: FS-AK reduced the refractive astigmatism at final follow-up visit at 12 months (p = 0.0008, repeated-measures analysis of variance [ANOVA]). The procedure improved the UCVA over the follow-up period (p = 0.007, repeated-measures ANOVA), with a similar effect on the BCVA (p = 0.046, repeated-measures ANOVA). There was a mild correlation between the target-induced astigmatism and the surgically induced astigmatism (R2 = 0.245) with a tendency to overcorrect more than under correct the astigmatism. A constant rotational error in the counterclockwise direction was also detected. CONCLUSIONS: FS-AK improves the visual outcome and reduces the refractive cylinder in post-penetrating keratoplasty astigmatism. The predictability of astigmatism correction was variable in reducing post-keratoplasty astigmatism. Refinement of the treatment nomogram for such cases is highly recommended.


Subject(s)
Astigmatism/surgery , Keratoplasty, Penetrating/adverse effects , Keratotomy, Radial/methods , Laser Therapy/methods , Adolescent , Adult , Analysis of Variance , Child , Female , Humans , Male , Middle Aged , Postoperative Complications/surgery , Prospective Studies , Visual Acuity
12.
J Agric Food Chem ; 67(23): 6497-6507, 2019 Jun 12.
Article in English | MEDLINE | ID: mdl-31083936

ABSTRACT

This experiment was to enrich docosahexaenoic acid (DHA) in broiler tissues through feeding a DHA-rich microalgal biomass and to explore the underlying metabolic and molecular mechanisms. Hatchling Cornish male broilers (total = 192) were fed a corn-soybean meal basal diet containing a full-fatted microalgae ( Aurantiochytrium) at 0%, 1%, 2%, and 4% for 6 weeks ( n = 6 cages/treatment, 8 birds/cage). The inclusion of microalgae led to dose-dependent ( P < 0.01) enrichments of DHA and decreases ( P < 0.01) of n-6/n-3 fatty acids (FAs) in plasma, liver, muscle, and adipose tissue. The microalgae supplementation also lowered ( P < 0.05-0.1) nonesterified FAs concentrations in the plasma, liver and adipose tissue. The mRNA abundances of most assayed genes involved in lipid metabolism were decreased ( P < 0.05) in the liver but elevated ( P < 0.05) in the adipose in response to the biomass supplementation. In conclusion, the biomass-resultant DHA enrichments in the broiler tissues were associated with a distinctive difference in the expression of lipid metabolism-controlling genes between the liver and adipose tissue.


Subject(s)
Animal Feed/analysis , Chickens/metabolism , Dietary Supplements/analysis , Docosahexaenoic Acids/metabolism , Fatty Acids/metabolism , Microalgae/metabolism , Stramenopiles/metabolism , Adipose Tissue/metabolism , Animal Nutritional Physiological Phenomena , Animals , Chickens/genetics , Fatty Acids/chemistry , Female , Liver/metabolism , Male , Microalgae/chemistry , Muscles/metabolism , Stramenopiles/chemistry
13.
Med Princ Pract ; 27(3): 267-271, 2018.
Article in English | MEDLINE | ID: mdl-29514164

ABSTRACT

OBJECTIVE: The aim of the present study was to evaluate anti-inflammatory activity of methanolic extract of Terminalia coriacea. MATERIALS AND METHODS: A methanolic extract of T. coriacea leaves was studied in albino Wistar rats with carrageenan-induced paw edema, an acute model, and cotton pellet-induced granuloma, a chronic model, at 3 oral test doses (125, 250, and 500 mg/kg). Aspirin 100 mg/kg was used as a positive control. Paw volume and wet and dry weights of cotton pellets were determined. The data were analyzed by one-way ANOVA followed by Dunnett's multiple comparison test. RESULTS: The test extract at doses of 125 and 250 mg/kg decreased paw volume and wet and dry weights of cotton pellets. The highest test dose (500 mg/kg) displayed a response comparable to that of the standard drug (p < 0.01) on paw volume. The extract produced similar (p < 0.05) decrease in wet weight of the cotton pellet at 125 and 250 mg/kg, whereas the effect of 500 mg/kg of the extract was comparable to that of aspirin 100 mg/kg (p < 0.01). The extract of T. coriacea at 500 mg/kg induced the most significant (p < 0.01) effect on wet weight of granulomatous tissue. CONCLUSION: The methanolic extract of T. coriacea leaves successfully decreased paw edema as well as dry and wet weights of granulomatous tissue in both acute and chronic inflammatory models thus confirming the anti- edematogenic, antitransudative, and antiproliferative properties of T. coriacea.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Edema/drug therapy , Granuloma/drug therapy , Plant Extracts/pharmacology , Terminalia , Animals , Aspirin/pharmacology , Disease Models, Animal , Dose-Response Relationship, Drug , Edema/chemically induced , Granuloma/chemically induced , Male , Phytotherapy/methods , Rats , Rats, Wistar
14.
Interact Cardiovasc Thorac Surg ; 25(4): 651-653, 2017 10 01.
Article in English | MEDLINE | ID: mdl-28591868

ABSTRACT

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was in [patients undergoing video-assisted thoracoscopic thymectomy for myasthenia gravis (MG)] is a [left-sided approach] superior to a [right-sided approach] in terms of [clinical outcome]? Two hundred and fifty-nine papers were found using the reported search. In looking at both procedures, we selected studies with a sizeable number of patients performing or studying both procedures and comparing their outcome. Hence, only 4 studies represented the best evidence to answer the clinical question. The authors, journal, date, country, study type, patient group, relevant outcomes and results of these papers are tabulated. Two studies compared their clinical experience with a right-sided versus a left-sided video assisted thoracoscopic surgery thymectomy approach, while 1 study compared using a bilateral versus a unilateral right-sided approach in patients with non-thymomatous MG. The number of patients studied included 31, 107 and 103 patients, respectively. All 3 studies demonstrated no difference regarding surgical time, intraoperative blood loss, postoperative hospital stay, postoperative complications and therapeutic effects (the last study compared the 5-year complete stable remission rate). All 3 studies concluded that both approaches are feasible, effective and comparable in operative and long-term results for the treatment of non-thymomatous MG. One anatomical study compared both approaches in 10 cadavers, 5 in each group. They studied the size of the specimen resected and visualization of different anatomic sites via each approach. Visualization was superior using the left-sided approach, while a right-sided approach resulted in slightly higher chances of an incomplete resection. The study concluded that a left-sided approach achieves a better chance of radical thoracoscopic thymectomy due to anatomic considerations. In conclusion, despite 1 cadaveric study suggesting that a left-sided approach may achieve more complete resection, possibly due to anatomical considerations, there are no differences in outcomes with either unilateral approach in terms of complications, hospital stay or long-term symptom relief.


Subject(s)
Myasthenia Gravis/surgery , Thoracic Surgery, Video-Assisted/methods , Thymectomy/methods , Thymus Gland/surgery , Female , Humans , Myasthenia Gravis/etiology , Thymus Gland/anatomy & histology , Young Adult
15.
J Nanobiotechnology ; 15(1): 24, 2017 Mar 29.
Article in English | MEDLINE | ID: mdl-28356160

ABSTRACT

BACKGROUND: Mesenchymal stromal cells (MSCs) have an inherent migratory capacity towards tumor tissue in vivo. With the future objective to quantify the tumor homing efficacy of MSCs, as first step in this direction we investigated the use of inorganic nanoparticles (NPs), in particular ca. 4 nm-sized Au NPs, for MSC labeling. Time dependent uptake efficiencies of NPs at different exposure concentrations and times were determined via inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: The labeling efficiency of the MSCs was determined in terms of the amount of exocytosed NPs versus the amount of initially endocytosed NPs, demonstrating that at high concentrations the internalized Au NPs were exocytosed over time, leading to continuous exhaustion. While exposure to NPs did not significantly impair cell viability or expression of surface markers, even at high dose levels, MSCs were significantly affected in their proliferation and migration potential. These results demonstrate that proliferation or migration assays are more suitable to evaluate whether labeling of MSCs with certain amounts of NPs exerts distress on cells. However, despite optimized conditions the labeling efficiency varied considerably in MSC lots from different donors, indicating cell specific loading capacities for NPs. Finally, we determined the detection limits of Au NP-labeled MSCs within murine tissue employing ICP-MS and demonstrate the distribution and homing of NP labeled MSCs in vivo. CONCLUSION: Although large amounts of NPs improve contrast for imaging, duration and extend of labeling needs to be adjusted carefully to avoid functional deficits in MSCs. We established an optimized labeling strategy for human MSCs with Au NPs that preserves their migratory capacity in vivo.


Subject(s)
Cell Tracking , Gold/chemistry , Mesenchymal Stem Cells/cytology , Metal Nanoparticles/chemistry , Animals , Cell Differentiation , Cell Movement , Cell Survival , Cells, Cultured , Endocytosis , Exocytosis , Humans , Male , Mass Spectrometry , Mice , Mice, Inbred BALB C , Particle Size
16.
J Med Chem ; 59(6): 2660-73, 2016 Mar 24.
Article in English | MEDLINE | ID: mdl-26894427

ABSTRACT

The feasibility of developing a single agent that can deliver radioactive iodine and also direct cellular immune function by engaging endogenous antibodies as an antibody-recruiting small molecule (ARM) was determined. A library of new prostate-specific membrane antigen (PSMA)-binding ligands that contained antibody-recruiting 2,4-dinitrophenyl (DNP) groups and iodine were synthesized and screened in vitro and in vivo. A lead compound (9b) showed high affinity for PSMA and the ability to bind anti-DNP antibodies. Biodistribution studies of the iodine-125 analogue showed 3% ID/g in LNCaP xenograft tumors at 1 h postinjection with tumor-to-blood and tumor-to-muscle ratios of 10:1 and 44:1, respectively. The radiolabeled analogue was bound and internalized by LNCaP cells, with both functions blocked using a known PSMA inhibitor. A second candidate showed high tumor uptake (>10% ID/g) but had minimal binding to anti-DNP antibodies. The compounds reported represent the first examples of small molecules developed specifically for combination immunotherapy and radiotherapy for prostate cancer.


Subject(s)
Antigens, Neoplasm/drug effects , Prostate-Specific Antigen/immunology , Prostatic Neoplasms/therapy , Radioimmunotherapy/methods , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/pharmacology , Animals , Cell Line, Tumor , Dinitrophenols/chemical synthesis , Dinitrophenols/pharmacology , Female , Humans , Ligands , Male , Mice , Mice, Nude , Prostatic Neoplasms/metabolism , Radiopharmaceuticals/pharmacokinetics , Small Molecule Libraries , Tissue Distribution , Xenograft Model Antitumor Assays
17.
Chinese Journal of Cancer ; (12): 356-364, 2014.
Article in English | WPRIM (Western Pacific) | ID: wpr-320524

ABSTRACT

3-Bromopyruvate (3BP) is a new, promising anticancer alkylating agent with several notable functions. In addition to inhibiting key glycolysis enzymes including hexokinase II and lactate dehydrogenase (LDH), 3BP also selectively inhibits mitochondrial oxidative phosphorylation, angiogenesis, and energy production in cancer cells. Moreover, 3BP induces hydrogen peroxide generation in cancer cells (oxidative stress effect) and competes with the LDH substrates pyruvate and lactate. There is only one published human clinical study showing that 3BP was effective in treating fibrolamellar hepatocellular carcinoma. LDH is a good measure for tumor evaluation and predicts the outcome of treatment better than the presence of a residual tumor mass. According to the Warburg effect, LDH is responsible for lactate synthesis, which facilitates cancer cell survival, progression, aggressiveness, metastasis, and angiogenesis. Lactate produced through LDH activity fuels aerobic cell populations inside tumors via metabolic symbiosis. In melanoma, the most deadly skin cancer, 3BP induced necrotic cell death in sensitive cells, whereas high glutathione (GSH) content made other melanoma cells resistant to 3BP. Concurrent use of a GSH depletor with 3BP killed resistant melanoma cells. Survival of melanoma patients was inversely associated with high serum LDH levels, which was reported to be highly predictive of melanoma treatment in randomized clinical trials. Here, we report a 28-year-old man presented with stage IV metastatic melanoma affecting the back, left pleura, and lung. The disease caused total destruction of the left lung and a high serum LDH level (4,283 U/L). After ethics committee approval and written patient consent, the patient received 3BP intravenous infusions (1-2.2 mg/kg), but the anticancer effect was minimal as indicated by a high serum LDH level. This may have been due to high tumor GSH content. On combining oral paracetamol, which depletes tumor GSH, with 3BP treatment, serum LDH level dropped maximally. Although a slow intravenous infusion of 3BP appeared to have minimal cytotoxicity, its anticancer efficacy via this delivery method was low. This was possibly due to high tumor GSH content, which was increased after concurrent use of the GSH depletor paracetamol. If the anticancer effectiveness of 3BP is less than expected, the combination with paracetamol may be needed to sensitize cancer cells to 3BP-induced effects.


Subject(s)
Adult , Humans , Male , Acetaminophen , Therapeutic Uses , Carcinoma, Hepatocellular , Disease Progression , Drug Therapy, Combination , Enzyme Inhibitors , Glutathione , Glycolysis , Hexokinase , L-Lactate Dehydrogenase , Lactic Acid , Lung Neoplasms , Melanoma , Drug Therapy , Necrosis , Neovascularization, Pathologic , Pleural Neoplasms , Prognosis , Pyruvates , Therapeutic Uses , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL