Role of NF-κB/IL-1β Pathway and Caspase 3 in Mediating the Hepatoprotective Effect of Rutin against Paraquat-Induced Liver Toxicity in Male Rats

One of the most common bipyridinium herbicides that can lead to liver toxicity is paraquat. Rutin is a bioflavonoid with antioxidant, anti-inflammatory, anti-hepatotoxic, and antimicrobial properties. The effect of rutin on paraquat-induced liver toxicity was examined in this study. 48 male rats were divided into six groups: the control group was given a normal diet; the non-treated group was given paraquat; the positive control group was given paraquat, and silymarin and the treatment groups were given paraquat and rutin at doses of 25, 50, and 100 mg/kg. After fourteen days, the rats were anesthetized by xylazine-ketamine, and fasting blood samples were obtained from their hearts to measure alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT), malondialdehyde (MDA), creatinine, lipid profile, antioxidant capacity, and carbonyl protein. The liver tissue was removed to measure the levels of catalase (CAT), superoxide dismutase (SOD), total protein, vitamin C, plus NF-κB, IL1β, and caspase-3 gene expressions. Paraquat gavage in the untreated group (group 2) for 14 days in comparison with the control group induced a significant augmentation (p<0.05) in levels of lipid profile, AST, ALP, ALT, MDA, carbonyl protein, and also NF-κB, IL1β, Caspase3 expressions. Treatment with rutin reduced the factors as mentioned above. Paraquat poisoning induced a substantial decline (p<0.05) in HDL content, FRAP level, CAT, and SOD activity of the liver compared to the control group. However, rutin oral treatment led to a substantial increase (p<0.05) in the level of these factors compared to the paraquat-only treated group. Based on the findings of the present study, it was found that rutin can be significantly effective in improving hepatotoxicity caused by paraquat.     

D-limonene nanoemulsion: lousicidal activity,stability, and effect on the cuticle of Columbicola columbae

The current study was conducted to investigate the efficacy and stability of D-limonene (DL) and its nanoemulsion (DLN) against pigeon feather lice (Columbicola columbae) and their mode of action. DL pure form and DLN were prepared and characterized freshly and after storage for 50 days. In vitro bioassay on live lice was conducted with different concentrations of DL, DLN, and deltamethrin (DM). The results revealed significant mortality rates in the DL-, DLN-, DM-treated groups when compared with the control (p < 0.05). The scanning electron micrographs of lice treated with DL and DLN revealed collapsed bodies with destruction in the cuticle of the mouthparts and damaged antennae. The 50 days stored DLN showed stability in their effectiveness when compared with the freshly prepared formulation. DL and DLN caused significant inhibition (p ≤ 0.05) in acetylcholinesterase activity (AchE). Malondialdehyde level (MDA) was significantly increased while glutathione was significantly decreased in DL- and DLN-treated lice. In conclusion, DL and DLN have significant lousicidal activities. DLN showed better stability than DL after storage for 50 days. In addition, the mode of action of DL may associate with its effect on the cuticle of the lice body, inhibition of AchE, and increasing oxidative stress in the treated lice.     

Silicon Enhances Morpho–Physio–Biochemical Responses in Arsenic Stressed Spinach (Spinacia oleracea L.) by Minimizing Its Uptake

Journal of Plant Growth Regulation - Soil contamination with toxic heavy metals [such as arsenic (As)] is becoming a serious global problem due to rapid development of social economy. Silicon (Si),...     

Introducing Circulating Vasculature-Related Transcripts as Biomarkers in Coronary Artery Disease

Molecular Diagnosis & Therapy - Atherosclerotic plaque is considered the hallmark of atherosclerotic lesions in coronary atherosclerosis (CAS), the primary pathogenesis in coronary artery...     

Adaptation supports short-term memory in a visual change detection task

The maintenance of short-term memories is critical for survival in a dynamically changing world. Previous studies suggest that this memory can be stored in the form of persistent neural activity or using a synaptic mechanism, such as with short-term plasticity. Here, we compare the predictions of these two mechanisms to neural and behavioral measurements in a visual change detection task. Mice were trained to respond to changes in a repeated sequence of natural images while neural activity was recorded using two-photon calcium imaging. We also trained two types of artificial neural networks on the same change detection task as the mice. Following fixed pre-processing using a pretrained convolutional neural network, either a recurrent neural network (RNN) or a feedforward neural network with short-term synaptic depression (STPNet) was trained to the same level of performance as the mice. While both networks are able to learn the task, the STPNet model contains units whose activity are more similar to the in vivo data and produces errors which are more similar to the mice. When images are omitted, an unexpected perturbation which was absent during training, mice often do not respond to the omission but are more likely to respond to the subsequent image. Unlike the RNN model, STPNet produces a similar pattern of behavior. These results suggest that simple neural adaptation mechanisms may serve as an important bottom-up memory signal in this task, which can be used by downstream areas in the decision-making process.     

SNP array-based homozygosity mapping reveals MCPH1 deletion in family with autosomal recessive mental retardation and mild microcephaly

Very little is known about the molecular basis of autosomal recessive MR (ARMR) because in developed countries, small family sizes preclude mapping and identification of the relevant gene defects. We therefore chose to investigate genetic causes of ARMR in large consanguineous Iranian families. This study reports on a family with six mentally retarded members. Array-based homozygosity mapping and high-resolution microarray-based comparative genomic hybridization (array CGH) revealed a deletion of approximately 150–200 kb, encompassing the promoter and the first six exons of the MCPH1 gene, one out of four genes that have been previously implicated in ARMR with microcephaly. Reexamination of affected individuals revealed a high proportion of prematurely condensed chromosomes, which is a hallmark of this condition, but in spite of the severity of the mutation, all patients showed only borderline to mild microcephaly. Therefore the phenotypic spectrum of MCPH1 mutations may be wider than previously assumed, with ARMR being the only consistent clinical finding.     

Substituted phenanthrenes with basic amino side chains: a new series of anti-breast cancer agents

In the course of our search for new anti-breast cancer agents, substituted phenanthrenes with basic amino side chains were synthesized and some of them showed remarkable antiproliferative activity against ER +ve MCF-7 cell line with IC(50) in the range of 3.53-22.25 microM. One of the compounds 15 ca showed anti-breast cancer activity in 7,12-dimethylbenz[a]anthracene (DMBA) induced hormone-dependent mammary tumor in rat and the activity was comparable to that shown by tamoxifen.     

Synthesis and biological evaluation of 2-amino-3-(3',4',5'-trimethoxybenzoyl)-6-substituted-4,5,6,7-tetrahydrothieno[2,3-c]pyridine derivatives as antimitotic agents and inhibitors of tubulin polymerization

Microtubules are among the most successful targets of compounds potentially useful for cancer therapy. A new series of inhibitors of tubulin polymerization based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)-4,5,6,7-tetrahydrothieno[b]pyridine molecular skeleton was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. The most promising compound in this series was 2-amino-3-(3,4,5-trimethoxybenzoyl)-6-methoxycarbonyl-4,5,6,7-tetrahydrothieno[b]pyridine, which inhibits cancer cell growth with IC(50)-values ranging from 25 to 90 nM against a panel of four cancer cell lines, and interacts strongly with tubulin by binding to the colchicine site. In this series of N(6)-carbamate derivatives, any further increase in the length and in the size of the alkyl chain resulted in reduced activity.     

Inhibition of monoamine oxidase-A activity in rat brain by synthetic hydrazines: structure-activity relationship (SAR)

A series of hydrazine derivatives was synthesized in order to evaluate their monoamine oxidase A (MAO-A) inhibitory effects. MAO-A inhibitory activity of 4-tosyl benzoic acid carbohydrazide was quite potent, similarly to that of the corresponding 4-benzyloxy-benzoic acid carbohydrazide and its N-cyanoethylated derivative. Structural variations of these compounds, such as the replacement of the 4-substitutent, of the aromatic ring on which the carbohydrazide moiety is grafted, as well as cyclization of the hydrazide moiety in five- or six-membered rings caused either significant decline or complete loss of MAO inhibitory properties. The most active compound (4-tosyl benzoic acid carbohydrazide) was also subjected to the forced swim test, an animal model of depression, eliciting a marked reduction in immobility time in rats, without affecting the locomotor activity, implying that it possesses anti-depressant properties due to inhibition of MAO type-A.