Antimicrobial and antiviral screening of novel indole carboxamide and propanamide derivatives

A few series of indole derivatives were screened for antimicrobial, antifungal and anti-HBV activities. The compounds were tested for their in vitro antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and for their antifungal activity against Candida albicans using a disc diffusion method, which measures the diameter of the inhibition zone around a paper disc soaked in a solution of the test compounds. The antimicrobial activity results showed that all compounds are as a active as the standard compound ampicillin against Staphylococcus aureus. It was also found that indole carboxamide derivatives, substituted at 3-position with several benzyl groups, showed better inhibition of Bacillus subtilis than their congeners substituted at 2-position. Activity patterns of the compounds against Escherichia coli and Staphylococcus aureus were found slightly different by the same method. In this case, there was no correlation between structure and activity of the compounds. The antifungal activity of carboxamide derivatives was found higher compared to that of the propanamide derivatives. The minimum inhibitory concentration (MIC) values of some indole derivatives were also determined by the tube dilution technique. The MIC values of the compounds were found nearly 20- to 100-fold smaller compared to the standard compounds ciprofloxacin and ampicillin (1.56-3.13 microg/ml and 1.56-12.5 microg/ml, respectively) against Staphylococcus aureus, Bacillus subtilis and Escherichia coli. The MIC values of the tested compounds showed that these are better inhibitors for Candida albicans. Indole derivatives were screened by the anti-HBV susceptibility test. No compound showed good inhibition against the HBV virus.     

Co-culture of rat luteal cells with islet cells enhances islet viability and revascularization

Islet cell transplantation is a major treatment strategy for type I diabetes, and has proven to be effective for maintaining glucose homeostasis. However, this treatment requires an extended period of immunosuppression to prevent rejection and recurrent transplantation to maintain function. Thus, to enhance the properties of transplanted islet cells, we examined the effect of the co-culture of luteal cells, which secrete progesterone, on islet cell viability, functionality, and revascularization. It was found that islet viability and functionality were higher in the co-cultured group than in single cultures of islets at 48 and 96 h, in parallel with increased progesterone and vascular endothelial growth factor (VEGF) secretion from luteal cells. In the co-culture groups, VEGF levels at 48 and 96 h and CD31 levels at 48 h were significantly higher than those in the islet groups (p?<?0.001 and p?<?0.05, respectively), and basic fibroblast growth factor (bFGF) levels were increased at 96 h (p?<?0.001). Thus, co-culture with luteal cells may increase islet vascularity by enhancing VEGF and bFGF levels for up to 96 h, which could help to markedly increase the pre-transplantation time to allow for effective immunosuppression therapy. This method may also promote islet cell viability and functionality. Progesterone and angiogenic factors secreted from luteal cells may be responsible for these positive effects.     

Ent-2α-hydroxy-13-epi-manoyl oxide from Sideritis perfoliata

A new ent-13-epi-manoyl oxide derivative was isolated from the aerial part of Sideritis perfoliata. Its structure, ent-2α-hydroxy-8,13β-epoxy-labd-14-ene, was established by chemical and spectroscopic means.     

Collective Cell Migration in Embryogenesis Follows the Laws of Wetting

Collective cell migration is a fundamental process during embryogenesis and its initial occurrence, called epiboly, is an excellent in vivo model to study the physical processes involved in collective cell movements that are key to understanding organ formation, cancer invasion, and wound healing. In zebrafish, epiboly starts with a cluster of cells at one pole of the spherical embryo. These cells are actively spreading in a continuous movement toward its other pole until they fully cover the yolk. Inspired by the physics of wetting, we determine the contact angle between the cells and the yolk during epiboly. By choosing a wetting approach, the relevant scale for this investigation is the tissue level, which is in contrast to other recent work. Similar to the case of a liquid drop on a surface, one observes three interfaces that carry mechanical tension. Assuming that interfacial force balance holds during the quasi-static spreading process, we employ the physics of wetting to predict the temporal change of the contact angle. Although the experimental values vary dramatically, the model allows us to rescale all measured contact-angle dynamics onto a single master curve explaining the collective cell movement. Thus, we describe the fundamental and complex developmental mechanism at the onset of embryogenesis by only three main parameters: the offset tension strength, α, that gives the strength of interfacial tension compared to other force-generating mechanisms; the tension ratio, δ, between the different interfaces; and the rate of tension variation, λ, which determines the timescale of the whole process.     

Circulating levels of apoptotic markers and oxidative stress parameters in women with polycystic ovary syndrome: a case-controlled descriptive study

Context: Apoptotic dysregulation plays a role in the pathogenesis of polycystic ovary syndrome (PCOS).

Objective: To evaluate circulatory apoptotic markers and oxidative stress in patients with PCOS.

Materials and methods: Forty-four women with PCOS, and 44 healthy women as controls were enrolled in the study. Oxidative stress parameters and caspases levels were measured in serum.

Results: The caspase 9 level was significantly lower and related with oxidant status in patients with PCOS, while the circulating levels of caspases 3 and 7 were statistically similar in both groups.

Discussion: This study is the first report demonstrating the circulating levels of apoptotic markers and their relationship with oxidant status in PCOS.

Conclusion: The circulating caspase 9 and oxidant status might contribute to apoptotic dysregulation in PCOS.     

Disruption of PTPRO causes childhood-onset nephrotic syndrome

Idiopathic nephrotic syndrome (INS) is a genetically heterogeneous group of disorders characterized by proteinuria, hypoalbuminemia, and edema. Because it typically results in end-stage kidney disease, the steroid-resistant subtype (SRNS) of INS is especially important when it occurs in children. The present study included 29 affected and 22 normal individuals from 17 SRNS families; genome-wide analysis was performed with Affymetrix 250K SNP arrays followed by homozygosity mapping. A large homozygous stretch on chromosomal region 12p12 was identified in one consanguineous family with two affected siblings. Direct sequencing of protein tyrosine phosphatase receptor type O (PTPRO; also known as glomerular epithelial protein-1 [GLEPP1]) showed homozygous c.2627+1G>T donor splice-site mutation. This mutation causes skipping of the evolutionarily conserved exon 16 (p.Glu854_Trp876del) at the RNA level. Immunohistochemistry with GLEPP1 antibody showed a similar staining pattern in the podocytes of the diseased and control kidney tissues. We used a highly polymorphic intragenic DNA marker-D12S1303-to search for homozygosity in 120 Turkish and 13 non-Turkish individuals in the PodoNet registry. This analysis yielded 17 candidate families, and a distinct homozygous c.2745+1G>A donor splice-site mutation in PTPRO was further identified via DNA sequencing in a second Turkish family. This mutation causes skipping of exon 19, and this introduces a premature stop codon at the very beginning of exon 20 (p.Asn888Lysfs*3) and causes degradation of mRNA via nonsense-mediated decay. Immunohistochemical analysis showed complete absence of immunoreactive PTPRO. Ultrastructural alterations, such as diffuse foot process fusion and extensive microvillus transformation of podocytes, were observed via electron microscopy in both families. The present study introduces mutations in PTPRO as another cause of autosomal-recessive nephrotic syndrome.     

Effect of cellulase,phytase and pectinase supplementation on growth performance and nutrient digestibility of rainbow trout (Oncorhynchus mykiss,Walbaum 1792) fry fed diets containing canola meal

This experiment was conducted to evaluate the effects of supplementing exogenous enzymes on growth, feed conversion ratio (FCR) and apparent nutrient digestibility in rainbow trout (Oncorhynchus mykiss) fry diets containing 32% canola meal. Five experimental diets (including a control diet containing no enzymes) were prepared as isonitrogenous (44% crude protein) and isocaloric (4000 kcal DE kg¹). The four other diets contained either cellulase, phytase, pectinase or an enzyme mix (a mixture of cellulase, phytase and pectinase in the same ratio). The feeding trial was conducted in triplicate for 12 weeks in 15 tanks (100‐L). At the beginning of the experiment 20 rainbow trout fry (initial weight 1.23 g) were stocked into each tank. Mean water temperature in the rearing tanks was 11°C and water flow in each tank was 6 L min^?1. At the end of the experiment the growth parameters and FCR displayed no significant differences in enzyme supplementation (P > 0.05). In addition, no differences were observed in dry matter, protein, or lipid digestibility with enzyme supplementation (P > 0.05). The results of this study showed that the addition of pectinase, phytase, cellulase or an enzyme mix to a diet containing 32% canola meal had no effect on growth, feed efficiency or dry matter, protein, or lipid digestibility in rainbow trout fry.     

Protective effect of Spirulina platensis against cell damage and apoptosis in hepatic tissue caused by high fat diet

Spirulina platensis is a microalga that may be a source of antioxidants that can reduce body fat deposition. Consumption of a high fat diet produces elevated blood lipid levels, inflammation and apoptosis. We investigated the possible effects of S. platensis on the blood lipid profile, and liver inflammation and apoptosis in rats fed a high fat diet. Sixty-four young male rats were divided into eight equal groups. The control group was fed a basic diet. The experimental groups were fed a diet for 60 days that was prepared by mixing variable amounts of 43% vegetable oil and 10% cholesterol with or without 3% S. platensis mixed with the basal diet. Blood and liver tissue samples were collected from each animal. Serum samples were used to analyze lipid parameters, total antioxidant status and total oxidant status. iNOS and eNOS were determined by immunohistochemistry. TUNEL staining was used to detect apoptosis to investigate a possible connection between inflammation and apoptosis in the liver tissue. The relations between fat deposition and liver degeneration were assessed by Sirius red staining and alpha-smooth muscle actin immunostaining. S. platensis reduced serum HDL-C, LDL-C and triglyceride, increased HDL-C levels in rats fed a high fat diet to near control levels, and reduced iNOS levels and increased eNOS levels in the liver tissue compared to vegetable oil and cholesterol treated groups. The apoptotic index was reduced in the groups that were fed a high fat or a basic diet when supplemented with S. platensis.     

Ex vivo protective effects of nicotinamide and 3‐aminobenzamide on rat synaptosomes treated with Aβ(1–42)

Alzheimer's disease (AD) is the most common form of dementia and is characterized by the presence of senile plaques and neurofibrillary tangles, along with synaptic loss. The underlying mechanisms of AD are not clarified yet, but oxidative stress and mitochondrial dysfunction are important factors. Overactivation of poly(adenosine diphosphate ribose) polymerase‐1 (PARP‐1) enzyme has been known to cause neuroinflammation and cell death in neurodegenerative processes. The aim of the present study was to investigate the protective effects of the PARP‐1 inhibitors, 3‐aminobenzamide (3‐AB) and nicotinamide (NA), against amyloid β peptide (1–42) (Aβ(1–42))‐induced oxidative damage and mitochondrial reduction capacity on isolated synaptosomes. Rats were injected intraperitoneally with 3‐AB (30–100 mg kg^?1), NA (100–500 mg kg^?1) or with saline for 7 days. Synaptosomes were incubated with 10–30 μM Aβ(1–42) or saline for 6 h at 37 °C. Ex vivo Aβ(1–42) treatment significantly induced oxidative stress and mitochondrial dysfunction in synaptosomes of the saline group, while synaptosomes of 3‐AB and NA groups showed significant decreases in lipid peroxidation, reactive oxygen species production and protein oxidation. Moreover, both NA and 3‐AB were able to improve the mitochondrial reduction capacity against Aβ(1–42). These data suggest that NA and 3‐AB may have protective effects in neurodegenerative processes because of the reduced levels of oxidative stress and the improvement of mitochondrial function. Copyright © 2014 John Wiley & Sons, Ltd.