Enhanced oral permeability of Trans-Resveratrol using nanocochleates for boosting anticancer efficacy; in-vitro and ex-vivo appraisal

Hepatocellular carcinoma (HCC) is a prevalent liver cancer representing the fourth most lethal cancer worldwide. Trans-Resveratrol (T-R) possesses a promising anticancer activity against HCC. However, it suffers from poor bioavailability because of the low solubility, chemical instability, and hepatic metabolism. Herein, we developed T-R-loaded nanocochleates using a simple trapping method. Nanocarriers were optimized using a comprehensive in-vitro characterization toolset and evaluated for the anticancer activity against HepG2 cell line. T-R-loaded nanocochleates demonstrated monodispersed cylinders (163.27 ± 2.68 nm and 0.25 ± 0.011 PDI) and −46.6 mV ζ-potential. They exhibited a controlled biphasic pattern with minimal burst followed by sustained release for 72 h. Significant enhancements of Caco-2 transport and ex-vivo intestinal permeation over liposomes, with 1.8 and 2.1-folds respectively, were observed. Nanocochleates showed significant reduction of 24 h IC50 values compared to liposomes and free T-R. Moreover, an efficient knockdown of anti-apoptotic (Bcl-2) and cancer stemness (NANOG) genes was demonstrated. To the best of our knowledge, we are the first to develop T-R loaded nanocochleates and scrutinize its potential in suppressing NANOG expression, 2-folds lower, compared to free T-R. According to these auspicious outcomes, nanocochleates represent a promising nanoplatform to enhance T-R oral permeability and augment its anticancer efficacy in the treatment of HCC

STEPS TOWARD OPTIMIZING HPGe DETECTOR EFFICIENCY IN THE CONTEXT OF LOW-LEVEL RADIOACTIVITY DETECTION

Different empirical and theoretical methods are used to precisely determine radionuclide activity concentrations. This study used Monte Carlo simulation MCNP5 code and EFFTRAN software (Efficiency Transfer) to determine the HPGe detector Full-Energy Peak (FEP) efficiency. A set of point sources (133Ba,152Eu,137Cs,60Co, and22Na) fixed on the top of the standard geometry plastic container were measured in order to obtain the calibration curve. Because of the importance of chemical composition parameters, the detector behavior due to different matrices was investigated. Experimental verification of the calibration was obtained using IAEA-TEL-2021-03 quality control water sample spiked with152Eu and133Ba, and the results were compared with reported results. A set of Certified Standard Reference samples were used for method validation. The obtained results were compared with the experimental results. The comparison clarified the advantages and disadvantages of both methods and their precision to demonstrate and suitable method for matrix types. © 2023, Publishing House of the Romanian Academy. All rights reserved

Increased endothelin-1 and diminished nitric oxide levels in blister fluids of patients with intermediate cold type complex regional pain syndrome type 1

BACKGROUND: In complex regional pain syndrome type 1 (CRPS1) pro-inflammatory mediators and vascular changes play an important role in the sustained development and outcome of the disease. The aim of this study was to determine the involvement of vasoactive substances endothelin-1 (ET-1) and nitric oxide (NO) during early chronic CRPS1. METHODS: Included were 29 patients with CRPS 1 who were diagnosed during the acute stage of their disease and observed during follow-up visits. Disease activity and impairment were determined and artificial suction blisters were made on the CRPS1 and the contralateral extremities for measurements of IL-6, TNF-α, ET-1 and nitrate/nitrite (NOx). RESULTS: The levels of IL-6, TNF-α and ET-1 in blister fluid in the CRPS1 extremity versus the contralateral extremity were significantly increased and correlated with each other, whereas NOx levels were decreased. CONCLUSION: The NOx/ET-1 ratio appears to be disturbed in the intermediate stage of CRPS, resulting in vasoconstriction and consequently in a diminished tissue blood distribution

Regulation of peripheral blood flow in Complex Regional Pain Syndrome: clinical implication for symptomatic relief and pain management

Background. During the chronic stage of Complex Regional Pain Syndrome (CRPS), impaired microcirculation is related to increased vasoconstriction, tissue hypoxia, and metabolic tissue acidosis in the affected limb. Several mechanisms may be responsible for the ischemia and pain in chronic cold CPRS. Discussion. The diminished blood flow may be caused by either sympathetic dysfunction, hypersensitivity to circulating catecholamines, or endothelial dysfunction. The pain may be of neuropathic, inflammatory, nociceptive, or functional nature, or of mixed origin. Summary. The origin of the pain should be the basis of the symptomatic therapy. Since the difference in temperature between both hands fluctuates over time in cold CRPS, when in doubt, the clinician should prioritize the patient's report of a persistent cold extremity over clinical tests that show no difference. Future research should focus on developing easily applied methods for clinical use to differentiate between central and peripheral blood flow regulation disorders in individual patients

Geochemistry and Utilization of Montmorillonitic Soil for Cationic Dye Removal

Geochemical studies of Egyptian soil-clay minerals from three different depths and their utilization as cationic dye adsorbents are presented. X-Ray diffraction patterns revealed that the dominant clay minerals in the studied samples were montmorillonite, kaolinite and illite. The ability of montmorillonitic soil samples to adsorb cationic dyes, namely Basic Blue 9 and Basic Red 18, was investigated at 30°C. The equilibrium adsorption data were well fitted to the Langmuir model and their parameters determined. The results showed that the adsorption capacity was dependent on the structure of the dyes and the geochemical features of the soil samples

Apoptotic markers in semen of infertile men: association with cigarette smoking

OBJECTIVES: (i) To examine the role of apoptosis in the pathogenesis of DNA damage in semen from infertile men. (ii) To assess the effects of smoking on apoptotic markers and seminal parameters among infertile men. (iii) To assess the correlation of apoptosis with conventional semen parameters. MATERIALS AND METHODS: The study was carried out on 70 men with idiopathic infertility, divided into two groups: thirty infertile non smokers and forty infertile smokers. In addition to 60 fertile men (30 non smokers and 30 smokers) as control group. Each subject provided semen for analysis of parameters, determination of % of DNA fragmentation, s-Fas, caspase-3 activity levels and cotinine levels. RESULTS: The results revealed that infertile men, particularly smokers have significantly lower semen variables and significantly higher levels of apoptotic variables (% of DNA fragmentation, s-Fas and caspase-3 activity) in addition to cotinine. CONCLUSIONS: The present findings provide additional evidence supporting the importance of the evaluation of apoptotic markers to test male infertility particularly among smokers

Urokinase plasminogen activator receptor, plasminogen activator inhibitor- 1,extracellular matrix metalloproteinase protein inducer and CA 15-3 as potential biomarkers for diagnosis and prognosis of primary breast cancer

Breast cancer is one of the most important leading causes of cancer deathin the less developed countries.The identification of markers that could assist in diagnosis, evaluation of therapeutic response, detection of recurrence and metastasis is a useful tool. The present study is undertaken to provide insights about the role of urokinase plasminogen activator receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), extracellular matrix metalloproteinase protein inducer (EMMPRIN), cancer antigen (CA) 15-3 in diagnosis and/or prognosis of breast cancer, evaluate the possible correlations between these biomarkers and the clinico-pathological status of breast cancer and compare between validity of these biomarkers with tumor marker (CA 15-3). A total of 75 women whose ages ranged between 30 to70 years and 10 healthy controls with matched age and sex were included. The patients were divided into 4 groups, group I: Included 39 female patients with breast cancer before operation, group II: Included 17 women from group I followed for 6 months after operation, group III: Included 9 women from group I followed for 12 months after operation, group IV: Included 10 female patients with benign breast diseases. Estimation of serum uPAR, PAI-1, EMMPRIN and CA 15-3 by ELISA and related clinico-pathological features were assessed. The results revealed higher mean serum levels of uPAR, PAI-1, EMMPRIN and CA 15-3 in breast cancer women before operation when compared to other 4 groups. Patients after 6 and 12 months follow up showed a decrement of uPAR, EMMPRIN, PAI-1 and CA 15-3 levels.There was significant relationbetween uPAR, PAI-1, EMMPRIN, CA 15-3 and clinicopathological characteristic of breast cancer patients. There was a significant positive correlation between serum uPAR, PAI-1 and EMMPRIN (p<0.001).In conclusion, High circulating uPAR, PAI-1 andEMMPRIN were significantly associated with breast carcinogenesis and metastasis. Accordingly, estimation of these biomarkers may predict the breast disease behavior and its prognosis.Key words:Breast cancer,CA 15-3,EMMPRIN, PAI-1, uPA

Pentraxin 3 genotyping in relation to serum levels of pentraxin 3 in patients with acute ST-segment elevation myocardial infarction

Objective: The aim of the study was to investigate the association of serum Pentraxin 3 and genotyping with the risk of developing AMI and its severity. Patients and methods: Fifty patients admitted to the coronary care unit presented with STEMI (acute ST segment myocardial infarction) at the Cardiology Department, Menoufia University Hospital in the period from October 2014 to April 2015 and another 20 subjects age- and gender-matched were taken as the control group. All patients and control groups were subjected to the following: Full history taking, complete clinical examination. ECG and echocardiography and Laboratory investigation including: estimation of lipid profile, urea and creatinine, CKMB, troponin I, serum pentraxin 3 and Genotyping of pentraxin 3 A/G SNP (rs2305619). Results: The patients with myocardial infarction had significantly higher levels of pentraxin 3 than the controls. The cut-off values for PTX3 and troponin I were 4.35 ng/ml and 0.34 μg/l respectively. Pentraxin 3 showed the highest diagnostic accuracy of coronary artery disease (96%), with sensitivity (96%) and specificity (95%). The highest serum pentraxin 3 levels were in the AA mutant homozygous type. Conclusion: PTX3 is one of the earliest biomarkers for detecting acute coronary syndrome. rs2305619 AA genotyping of the pentraxin 3 gene might be a candidate risk factor for development of coronary artery disease, presumably by increased pentraxin 3 levels

ON CLUSTER VALIDITY INDEXES IN FUZZY AND HARD CLUSTERING ALGORITHMS FOR IMAGE SEGMENTATION

This paper addresses the issue of assessing the quality of the clusters found by fuzzy and hard clustering algorithms. In particular, it seeks an answer to the question on how well cluster validity indexes can automatically determine the appropriate number of clusters that represent the data. The paper surveys several key existing solutions for cluster validity in the domain of image segmentation. In addition, it suggests two new indexes. The first one is based on Akaike’s information criterion (AIC). While AIC was devoted to other domains such as statistical estimation of model fitting, it is implemented here for the first time as a validation index. The second index is developed from the well-established idea of cross-validation. The existing and new indexes are evaluated and compared on several synthetic images corrupted with noise of varying levels and volumetric MR data. Index Terms—clustering, cluster validity, fuzzy clustering, image segmentation. 1