Design and synthesis of new fused carbazole-imidazole derivatives as anti-diabetic agents: In vitro α-glucosidase inhibition,kinetic, and in silico studies

Twenty three fused carbazole–imidazoles 6a–w were designed, synthesized, and screened as new α-glucosidase inhibitors. All the synthesized fused carbazole-imidazoles 6a-w were found to be more active than acarbose (IC₅₀?=?750.0?±?1.5?µM) against yeast α-glucosidase with IC₅₀ values in the range of 74.0?±?0.7–298.3?±?0.9?µM. Kinetic study of the most potent compound 6v demonstrated that this compound is a competitive inhibitor for α-glucosidase (K_i value?=?75?µM). Furthermore, the in silico studies of the most potent compounds 6v and 6o confirmed that these compounds interacted with the key residues in the active site of α-glucosidase.     

Hypocone reduction and Carabelli's traits in contemporary Jordanians and the association between Carabelli's trait and the dimensions of the maxillary first permanent molar

The objective of this study is to determine the prevalence of expression and bilateralism of two dental morphological traits in contemporary Jordanians: The hypocone reduction trait on the maxillary second permanent molar and Carabelli's trait on maxillary permanent first and second molars. Furthermore, inter-trait correlation and the relationship of Carabelli's traits with upper first molar dimensions were investigated. Three hundred subjects of school children at their 10th grade and of an average age of 15.5 +/- 0.4 years were involved. Alginate impressions for the maxillary arch were taken, dental casts were reproduced. The selected accurate casts were of 132 male- and 155 female-students. The frequencies of hypocone reduction trait on the maxillary second molar and Carabelli's trait on the maxillary molars were examined. Buccolingual and mesiodistal diameters of the maxillary first molar were measured and recorded. Paired Sample t test and Nonparametric Correlation analysis were used for data analysis. Hypocone reduction trait on the maxillary second molar was found in 29.8% of the examined students. Positive forms of Carabelli's trait on first and second molars were observed in 65.0% and 3.8%, respectively. Nonparametric correlation analysis revealed positive association between Carabelli's trait on first molar and hypocone reduction trait on the maxillary second molar. The presence of Carabelli's trait on first molar was strongly associated with the increase of buccolingual, but not the mesiodistal, diameter. Bilateralism was found highly significant in the tested traits and both genders (p < 0.001). This finding might be a sign of relatively low environmental stresses in the living Jordanian population and/or great ability of its individuals to buffer the adverse effects of such stresses.     

Phorate triggers oxidative stress and mitochondrial dysfunction to enhance micronuclei generation and DNA damage in human lymphocytes

Herein, we studied phorate for its toxicological effects in human lymphocytes. Phorate treatment for 3 h has induced significant increase in the lymphocytic DNA damage. Compared to control, comet data from highest concentration of phorate (1000 µM) showed 8.03-fold increase in the Olive tail moment (OTM). Cytokinesis blocked micronucleus (CBMN) assay revealed 6.4-fold increase in binucleated micronucleated (BNMN) cells following the exposure with phorate (200 µM) for 24 h. The nuclear division index (NDI) in phorate (200 µM) treated cells reduced to 1.8 vis-à-vis control cells showed NDI of 1.94. Comparative to untreated control, 60.43% greater DCF fluorescence was quantitated in lymphocytes treated with phorate (500 µM), affirming reactive oxygen species (ROS) generation and oxidative stress. Flow cytometric data of phorate (200 µM) treated lymphocytes showed 81.77% decline in the fluorescence of rhodamine 123 (Rh123) dye, confirming the perturbation of mitochondrial membrane potential (ΔΨm). Calf thymus DNA (ct-DNA) treated with phorate (1000 µM) exhibited 2.3-fold higher 8-Hydroxy-2′-deoxyguanosine (8-oxodG) DNA adduct formation, signified the oxidative DNA damage. The alkaline unwinding assay revealed 4.0 and 6.5 ct-DNA strand breaks when treated to phorate and phorate-Cu (II) complex. Overall, the data unequivocally suggests the cyto- and genotoxic potential of phorate in human lymphocytes, which may induce comparable toxicological consequences in persons occupationally or non-occupationally exposed to insecticide phorate.     

Biofabrication with chitosan

The traditional motivation for integrating biological components into microfabricated devices has been to create biosensors that meld the molecular recognition capabilities of biology with the signal processing capabilities of electronic devices. However, a different motivation is emerging; biological components are being explored to radically change how fabrication is achieved at the micro- and nanoscales. Here we review biofabrication, the use of biological materials for fabrication, and focus on three specific biofabrication approaches: directed assembly, where localized external stimuli are employed to guide assembly; enzymatic assembly, where selective biocatalysts are enlisted to build macromolecular structure; and self-assembly, where information internal to the biological material guides its own assembly. Also reviewed are recent results with the aminopolysaccharide chitosan, a material that offers a combination of properties uniquely suited for biofabrication. In particular, chitosan can be directed to assemble in response to locally applied electrical signals, and the chitosan backbone provides sites that can be employed for the assembly of proteins, nucleic acids, and virus particles.     

Heterogeneous effects of cholecystokinin on neuronal response properties in deep layers of rat barrel cortex

Abstract

Cholecystokinin (CCK) is one of the most studied neuropeptides in the brain. In this study, we investigated the effects of CCK-8s and LY225910 (CCK₂ receptor antagonist) on properties of neuronal response to natural stimuli (whisker deflection) in deep layers of rat barrel cortex. This study was done on 20 male Wistar rats, weighing 230–260?g. CCK-8s (300?nmol/rat) and LY225910 (1?µmol/rat) were administered intracerebroventricularly (ICV). Neuronal responses to deflection of principal (PW) and adjacent (AW) whiskers were recorded in the barrel cortex using tungsten microelectrodes. Computer controlled mechanical displacement was used to deflect whiskers individually or in combination at 30?ms inter-stimulus intervals. ON and OFF responses for PW and AW deflections were measured. A condition-test ratio (CTR) was computed to quantify neuronal responses to whisker interaction. ICV administration of CCK-8s and LY225910 had heterogeneous effects on neuronal spontaneous activity, ON and OFF responses to PW and/or AW deflections, and CTR for both ON and OFF responses. The results of this study demonstrated that CCK-8s can modulate neuronal response properties in deep layers of rat barrel cortex probably via CCK₂ receptors.     

Unconscious orientation processing

Recent findings have shown that certain attributes of visual stimuli, like orientation, are registered in cortical areas when the stimulus is unresolvable or perceptually invisible; however, there is no evidence to show that complex forms of orientation processing (e.g., modulatory effects of orientation on the processing of other features) could occur in the absence of awareness. To address these questions, different psychophysical paradigms were designed in six experiments to probe unconscious orientation processing. First we demonstrated orientation-selective adaptation and color-contingent orientation adaptation for peripheral unresolvable Gabor patches. The next experiments showed the modulatory effects of perceptually indiscriminable orientations on apparent motion processing and attentional mechanisms. Finally we investigated disappearance patterns of unresolvable Gabor stimuli during motion-induced blindness (MIB). Abrupt changes in local unresolvable orientations truncated MIB; however, orientation-based grouping failed to affect the MIB pattern when the orientations were unresolvable. Overall results revealed that unresolvable orientations substantially influence perception at multiple levels.     

Reproducibility of swallow-induced cortical BOLD positive and negative fMRI activity

Functional MRI (fMRI) studies have demonstrated that a number of brain regions (cingulate, insula, prefrontal, and sensory/motor cortices) display blood oxygen level-dependent (BOLD) positive activity during swallow. Negative BOLD activations and reproducibility of these activations have not been systematically studied. The aim of our study was to investigate the reproducibility of swallow-related cortical positive and negative BOLD activity across different fMRI sessions. We studied 16 healthy volunteers utilizing an fMRI event-related analysis. Individual analysis using a general linear model was used to remove undesirable signal changes correlated with motion, white matter, and cerebrospinal fluid. The group analysis used a mixed-effects multilevel model to identify active cortical regions. The volume and magnitude of a BOLD signal within each cluster was compared between the two study sessions. All subjects showed significant clustered BOLD activity within the known areas of cortical swallowing network across both sessions. The cross-correlation coefficient of percent fMRI signal change and the number of activated voxels across both positive and negative BOLD networks were similar between the two studies (r ≥ 0.87, P < 0.0001). Swallow-associated negative BOLD activity was comparable to the well-defined "default-mode" network, and positive BOLD activity had noticeable overlap with the previously described "task-positive" network. Swallow activates two parallel cortical networks. These include a positive and a negative BOLD network, respectively, correlated and anticorrelated with swallow stimulus. Group cortical activity maps, as well as extent and amplitude of activity induced by volitional swallowing in the cortical swallowing network, are reproducible between study sessions.     

Development of optical biosensor technologies for cardiac troponin recognition

Acute myocardial infarction (AMI) is the leading cause of death among cardiovascular diseases. Among the numerous attempts to develop coronary marker concepts into clinical strategies, cardiac troponin is known as a specific marker for coronary events. The cardiac troponin concentration level in blood has been shown to rise rapidly for 4–10 days after onset of AMI, making it an attractive approach for a long diagnosis window for detection. The extremely low clinical sensing range of cardiac troponin levels consequently makes the methods of detection highly sensitive. In this review, by taking into consideration optical methods applied for cardiac troponin detection, we discuss the most commonly used methods of optical immunosensing and provide an overview of the various diagnostic cardiac troponin immunosensors that have been employed for determination of cardiac troponin over the last several years.     

Age‐specific reference intervals for routine biochemical parameters in healthy neonates,infants, and young children in Iran

Age and sex need to be considered in the establishment of reference intervals (RIs), especially in early life when there are dynamic physiological changes. Since data for important biomarkers in healthy neonates and infants are limited, particularly in Iranian populations, we have determined age‐specific RIs for 7 laboratory biochemical parameters. This cross‐sectional study comprised a total of 344 paediatric participants (males: 158, females: 186) between the ages of 3 days and 30 months (mean age: 12.91 ± 7.15 months). Serum levels of creatinine, urea, uric acid, calcium, phosphate, vitamin D and high‐sensitivity C‐reactive protein (hs‐CRP) were measured using an Alpha classic‐AT plus auto‐analyser. We determined age‐specific RIs using CLSI Ep28‐A3 and C28‐A3 guidelines. No sex partitioning was required for any of the biomarkers. Age partitioning was required for kidney function tests and phosphate. The serum concentration of urea and creatinine increased with age, while phosphate and uric acid decreased with age. Age partitioning was not required for serum calcium, vitamin D, and hs‐CRP, which remained relatively constant throughout the age range. Age‐specific RIs for 7 routine biochemical markers were determined to address critical gaps in RIs in early life to help improve clinical interpretation of blood test results in young children, including neonates. Established age partitions demonstrate the biochemical changes that take place during child growth and development. These novel data will ultimately better disease management in the Iranian paediatric population and can be of value to clinical and hospital laboratories with similar populations.     

Response of field-grown chickpea (Cicer arietinum L.) to phosphorus fertilization for yield and nitrogen fixation

Application of phosphorus at 40, 60, 80 and 100 kg P₂O₅ ha^–1 in the presence of a uniform dressing of nitrogen (N) and potash (K₂O) each applied at 20 and 24 kg ha^–1 to chickpea (CM-88) grown in sandy loam soil in a replicated field experiment improved the nodulation response of the crop, increased its grain yield (ka ha^–1) by 18, 59, 40 and 14 percent, biomass yield (ka ha^–1) by 32, 32, 54 and 14 percent, biomass N (kg ha^–1) by 31, 48, 49, 19 percent, and biomass P (kg ha^–1) by 26, 40, 41 and 11 percent, respectively. The effect of phosphorus on the nitrogenase activity of the excised roots of chickpea was, however, inconsistent.