Feedback associative memory based on a new hybrid model of generalized regression and self-feedback neural networks

The focus of this paper is to propose a hybrid neural network model for associative recall of analog and digital patterns. This hybrid model consists of self-feedback neural network structures (SFNN) in parallel with generalized regression neural networks (GRNN). Using a new one-shot learning algorithm developed in the paper, pattern representations are first stored as the asymptotically stable fixed points of the SFNN. Then in the retrieving process, each pattern is applied to the GRNN to make the corresponding initial condition and to initiate the dynamical equations of the SFNN that should in turn output the corresponding representation. In this way, the corresponding stored patterns are retrieved even under high noise degradation. Moreover, contrary to many associative memories, the proposed hybrid model is without any spurious attractors and can store both binary and real-value patterns without any preprocessing. Several simulations confirm the theoretical analyses of the model. Results indicate that the performance of the hybrid model is better than that of recurrent associative memory and competitive with other classes of networks.     

Identification of miR-3182 and miR-3143 target genes involved in the cell cycle as a novel approach in TNBC treatment: A systems biology approach

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis, lacking therapeutic targets. miRNAs play crucial roles in TNBC through regulating various mechanisms, including cellular growth and proliferation. This study aims to identify critical target genes of two novel miRNAs (miR-3143 and miR-3182) involved in the cell cycle of TNBC as possible therapeutic targets and investigates their regulatory and therapeutic roles through a systems biology approach and in vitro experiment. Datasets related to the TNBC cell line (MDA-MB-231) were screened and retrieved, and Gene regulatory networks were constructed. Significant regulatory motifs were detected and analyzed using the FANMOD and Cytoscape analyzer, and the clusters and seeds were identified using the MCODE. Functional enrichment analysis was also performed using DAVID and STRING. The most critical genes were determined using the analysis of GRN motifs and PPI clusters. The essential genes involved in the cell cycle were selected and verified using the bc-GenExMiner v4.7. We overexpressed miR-3143 and miR-3182 in the MDA-MB-231 cell line using human umbilical cord mesenchymal stem cell (HUCMSC)-miRNA loaded exosomes, and the expression of the critical target genes was investigated using RT-qPCR. We identified eight critical genes as potential therapeutic targets. Their expression decreased by overexpression of miR-3143 and miR-3182 in RT-qPCR. The identified critical genes have probably significant roles in the pathogenesis of TNBC through the cell cycle. We suggest that the overexpression of miR-3143 and miR-3182 could be a new therapeutic candidate in TNBC and is worth more investigation.     

The effect of electromagnetic field on decreasing and increasing of the growth and proliferation rate of dermal fibroblast cell

Maintaining the health of dermal fibroblast cells and controlling their growth and proliferation would directly affect the health of skin tissues. The present study encompassed three control and three experimental specimens, which were different in terms of the duration of exposure to electromagnetic field (EMF) and intensity. With a decrease in intensity from 2 to 1 mT during 24, 48, and 72 h after exposing the cells to EMF, the frequency of the sample fibroblast cells increased by 60.3%, 144.9%, and 90.1%, respectively. With an increase in intensity from 3 to 4 mT during 48 and 72 h of exposure to EMF, the frequencies of the sample fibroblast cells decreased by 6.8% and 86.7%, respectively. It seems to be possible to achieve the most desirable condition to help the restoration of wounds and skin lesions through decreasing the exposure intensity from 2 to 0.5 mT and increasing EMF exposure time from 24 to 72 h simultaneously and non‐invasively. The most desirable approach to improve the treatment of skin cancers non‐invasively is to increase the intensity from 3 to 5 mT and to enhance EMF exposure time from 48 to 72 h.     

Metabolic effects of newly synthesized phosphodiesterase-3 inhibitor 6-[4-(4-methylpiperidin-1-yl)-4-oxobutoxy]-4-methylquinolin-2(1H)-one on rat adipocytes

Background

Clinical use of selective PDE3 inhibitors as cardiotonic agents is limited because of their chronotropic and lipolytic side effects. In our previous work, we synthesized a new PDE3 inhibitor named MC2 (6-[4-(4-methylpiperidin-1-yl)-4-oxobutoxy]-4-methylquinolin-2(1H)-one) which produced a high positive inotropic action with a negative chronotropic effect. This work was done to evaluate the effects of MC2 on adipocytes and compare its effects with those of amrinone and cilostamide.

Methods

Preadipocytes were isolated from rat adipose tissue and differentiated to adipocyte in the presence of cilostamide, amrinone or MC2. Lipolysis and adipogenesis was evaluated by measuring glycerol level and Oil Red O staining, respectively. Adipocyte proliferation and apoptosis were determined with MTT assay and Annexin V/PI staining, respectively.

Results

Differentiation to adipocyte was induced by amrinone but not by cilostamide or MC2. Basal and isoproterenol-stimulated lipolysis significantly increased by cilostamide (p < 0.05). Similarly, amrinone enhanced the stimulated lipolysis (p < 0.01). On the other hand, MC2 significantly decreased both adipogenesis (p < 0.05) and stimulated lipolysis (p < 0.001). Also, incubation of differentiated adipocytes with MC2 caused the loss of cell viability, which was associated with the elevation in apoptotic rate (p < 0.05).

Conclusion

Our data indicate that selective PDE3 inhibitors produce differential effects on adipogenesis and lipolysis. MC2 has proapoptotic and antilipolytic effects on adipocytes and does not stimulate adipogenesis. Therefore, in comparison with the clinically available selective PDE3 inhibitors, MC2 has lowest metabolic side effects and might be a good candidate for treatment of congestive heart failure.     

Evaluation of hematological and biochemical profiles in dairy cows with left displacement of the abomasum

For the present study, 25 Holstein and crossbreed, 3 to 7-year-old cows diagnosed with left displacement of the abomasum and 15 healthy cattle as control groups over a period of 2 years were used. LDA diagnosis was based on clinical examinations (high-pitched bell-like sounds) and confirmed by laparoscopy. Two blood samples were collected from each case through the jugular vein including one tube containing EDTA for hematological parameters analysis and one tube without anticoagulant for biochemical analysis. Hematological parameters including Ca, P, Mg, Cl, AST, urea, and glucose concentrations were measured by routine procedures. Serum was determined by use of an atomic absorption spectrophotometer, and Na and K values were obtained using a flame photometer. The results of this study showed that Hb, percentage of PCV, total leukocytic, neutrophils, total protein count plus AST, urea, and glucose concentrations were significantly increased in the LDA cases compared to the control group, whereas a marked decrease in plasma electrolyte concentrations (hyponatremia, hypochloremia, hypokalemia, and hypocalcemia) was found in 88–92% of LDA cases. In conclusion, in the present study, it was shown that DA causes alterations in the clinical, hematological, and biochemical profiles and these alterations can be more severe when DA is concurrent with other diseases.     

Determination of Cefixime by a Validated Stability-Indicating HPLC Method and Identification of its Related Substances by LC-MS/MS Studies

Cefixime is an important cephalosporin antibiotic that easily decomposes and releases different related substances in preparation and storage steps. The objective of the current study was to develop a simple, precise, and accurate isocratic liquid chromatography (LC) method for the determination of cefixime in the presence of its related substances generated from thermal stress in the bulk drug. The chromatographic conditions were comprised of a reversed-phase C18 column (4.6 × 250 mm, 5 μm) with a mobile phase composed of water: acetonitrile (85:15 v/v, with 0.5% formic acid) and ultraviolet detection (UV). Some thermal degradation products were identified using a proposed liquid chromatography-mass spectrometry method. Five peaks (A, B, C, D, and E impurities based on British Pharmacopoeia) were known and a few unknown peaks appeared in the thermal stress solution of cefixime. The linear regression analysis data for the calibration plot of the LC-UV method showed a good linear relationship in the concentration range 0.9–1000.0 μg mL⁻¹. The recovery of the optimized method was between 94.6 and 98.4% and the inter- and intra-day relative standard deviations were less than 3.3%. The obtained results shown in the LC-UV proposed method can be conveniently used in a quality control laboratory for routine analysis of cefixime for the assay and related substances, as well as for the evaluation of stability samples of bulk drugs.     

Relationship between Myocardial Viability and Coronary Run-Off in Jeopardized Myocardium

Abstract   Objective: The aim of this study was to evaluate the relationship between coronary run-off and myocardial viability in jeopardized regions. Method: We studied 50 patients (40 male, mean age: 55.63 ± 10.54 years) with coronary artery stenosis >70% and ejection fraction <40% referred for viability study via dobutamine stress echocardiography. The relationship between coronary run-off and viability was evaluated. Good run-off demonstrates good or moderate and no run-off means poor or no run-off. Results: In the apical region, 33% of the segments with good antegrade run-off were viable and 67% nonviable. Also, 72% of the segments with no run-off were nonviable and 28% viable. In the midportion region, 70% of the segments with good antegrade run-off were viable and 30% nonviable; 50% of the segments with no run-off were nonviable and 50% viable. In the basal region, 85% of the segments with good antegrade run-off were viable and 15% nonviable; 19% of the segments with no run-off were nonviable and 81% viable. The proportion of the nonviable segments increased significantly from the basal to apical regions either with good (p < 0.001) or no run-off (p = 0.004). From 239 viable segments, 58.6% had antegrade, 15.4% retrograde, and 25.5% no run-off. Of 181 nonviable segments, 44% had antegrade, 34% retrograde, and 34.8% no run-off. Conclusion: There was more susceptibility to nonviability in the apical regions despite good run-off, while the basal segments showed more viability in spite of having no run-off. The findings may be helpful for selecting patients with coronary artery disease and left ventricular systolic dysfunction that benefit from revascularization.     

Increases in food intake or food-seeking behavior induced by GABAergic,opioid, or dopaminergic stimulation of the nucleus accumbens: is it hunger?

Rationale Previous work has shown that stimulation of GABAergic, opioid, or dopaminergic systems within the nucleus accumbens modulates food intake and food-seeking behavior. However, it is not known whether such stimulation mimics a motivational state of food deprivation that commonly enables animals to learn a new operant response to obtain food.Objectives In order to address this question, acquisition of lever pressing for food in hungry animals was compared with acquisition in non-food-deprived rats subjected to various nucleus accumbens drug treatments.Methods All animals were given the opportunity to learn an instrumental response (a lever press) to obtain a food pellet. Prior to training, ad lib-fed rats were infused with the -aminobutyric acid (GABA)_A agonist muscimol (100 ng/0.5 µl per side) or the mu-opioid receptor agonist d-Ala², N-me-Phe⁴, Gly-ol⁵-enkephalin (DAMGO, 0.25 µg/0.5 µl per side), or saline into the nucleus accumbens shell (AcbSh). The indirect dopamine agonist amphetamine (10 µg/0.5 µl per side) was infused into the AcbSh or nucleus accumbens core (AcbC) of ad lib-fed rats. An additional group was food deprived and infused with saline in the AcbSh. Chow and sugar pellet intake responses after drug treatments were also evaluated in free-feeding tests.Results Muscimol, DAMGO, or amphetamine did not facilitate acquisition of lever pressing for food, despite clearly increasing food intake in free-feeding tests. In contrast, food-deprived animals rapidly learned the task.Conclusions These findings suggest that pharmacological stimulation of any of these neurochemical systems in isolation is insufficient to enable acquisition of a food-reinforced operant task. Thus, these selective processes, while likely involved in control of food intake and food-seeking behavior, appear unable to recapitulate the conditions necessary to mimic the state of negative energy balance.