Synthesis and structure-activity relationship studies of theophylline analogs on population responses in the rat hippocampus in vitro

We synthesized several theophylline analogs and tested the hypothesis that these compounds may be nootropic or cognitive enhancers by examining their effects on evoked population spikes recorded extracellularly in the CA1 region of the rat hippocampus. Whereas the length of the carbon chain on N7 had no effect, different size of the terminal lactam ring strongly influenced neuroactivity. Our results suggest that hexahydroazepin-2-one analogs have potential for further development as cognitive enhancers.     

Panax ginseng extract modulates oxidative stress,DNA fragmentation and up-regulate gene expression in rats sub chronically treated with aflatoxin B1 and fumonisin B1

Aflatoxins and fumonisins are important food-borne mycotoxins implicated in human health and have cytotoxic effects. The aims of the current study were to evaluate the protective role of Panax ginseng extract (PGE) against the synergistic effect of subchronic administration of aflatoxin B₁ (AFB₁) and fumonisin B₁ (FB₁) on DNA and gene expression in rat. Female Sprague–Dawley rats were divided into eight groups (ten rats/group) and treated for 12 weeks including the control group, the group having received AFB₁ (80 µg/kg bw), the group having received FB₁ (100 µg/kg bw), the group having received AFB₁ plus FB₁ and the groups having received PGE (20 mg/kg bw) alone or with AFB₁ and/or FB₁. At the end of experiment, liver and kidney were collected for the determination of DNA fragmentation, lipid peroxidation (LP), glutathione (GSH) contents and alterations in gene expression. The results indicated that these mycotoxins increased DNA fragmentation, LP and decreased GSH content in liver and kidney and down-regulated gene expression of antioxidants enzymes. The combined treatments with AFB₁ and/or FB₁ plus PGE suppressed DNA fragmentation only in the liver, normalized LP and increased GSH in the liver and kidney as well as up-regulated the expression of GPx, SOD1 and CAT mRNA. It could be concluded that AFB₁ and FB₁ have synergistic genotoxic effects. PGE induced protective effects against their oxidative stress and genotoxicity through its antioxidant properties.     

Peroxiredoxin IV plays a critical role in cancer cell growth and radioresistance through the activation of the Akt/GSK3 signaling pathways

High levels of redox enzymes have been commonly observed in various types of human cancer, although whether and how the enzymes contribute to cancer malignancy and therapeutic resistance have yet to be understood. Peroxiredoxin IV (Prx4) is an antioxidant with bona fide peroxidase and molecular chaperone functions. Here, we report that Prx4 is highly expressed in prostate cancer patient specimens, as well as established prostate cancer cell lines, and that its levels can be further stimulated through the activation of androgen receptor signaling. We used lentivirus-mediated shRNA knockdown and CRISPR-Cas9 based KO techniques to establish Prx4-depleted prostate cancer cells, which showed delayed cell cycle progression, reduced rate of cell proliferation, migration, and invasion compared to control cells. In addition, we used proteome profiler phosphokinase arrays to identify signaling changes in Prx4-depleted cells; we found that loss of Prx4 results in insufficient phosphorylation of both Akt and its downstream kinase GSK3α/β. Moreover, we demonstrate that Prx4-depleted cells are more sensitive to ionizing radiation as they display compromised ability to scavenge reactive oxygen species and increased accumulation of DNA damage. In mouse xenograft models, we show depletion of Prx4 leads to significant suppression of tumor growth, and tumors formed by Prx4-depleted cells respond more effectively to radiation therapy. Our findings suggest that increased levels of Prx4 contribute to the malignancy and radioresistance of prostate cancer through the activation of Akt/GSK3 signaling pathways. Therefore, strategies targeting Prx4 may be utilized to potentially inhibit tumor growth and overcome radioresistance in prostate cancer.     

A Possible Novel Protective Effect of Piceatannol against Isoproterenol (ISO)-Induced Histopathological,Histochemical, and Immunohistochemical Changes in Male Wistar Rats

Dry mouth is characterized by lower saliva production and changes in saliva composition. In patients with some salivary gland function remaining, pharmaceutical treatments are not recommended; therefore, new, more effective methods of promoting saliva production are needed. Hence, this study aimed to provide an overview of the histological changes in the salivary gland in the model of isoproterenol (ISO)-induced degenerative changes in male Wistar rats and to evaluate the protective effect of piceatannol. Thirty-two male Wistar rats were randomly divided into four groups: the control group, the ISO group, and the piceatannol (PIC)-1, and -2 groups. After the third day of the experiment, Iso (0.8 mg/100 g) was injected intraperitoneally (IP) twice daily into the animals. PIC was given IP in different daily doses (20 and 40 mg/kg) for three days before ISO and seven days with ISO injection. The salivary glands were rapidly dissected and processed for histological, histochemical, immunohistochemical (Ki-67), and morphometric analysis. Upon seven days of treatment with ISO, marked hypertrophy was observed, along with an increased number of positive Ki-67 cells. Proliferation was increased in some endothelial cells as well as in ducts themselves. Despite the significant decrease in proliferation activity, the control group did not return to the usual activity level after treatment with low-dose PIC. Treatment with a high dose of PIC reduced proliferative activity to the point where it was substantially identical to the results seen in the control group. An ISO-driven xerostomia model showed a novel protective effect of piceatannol. A new era of regenerative medicine is dawning around PIC’s promising role.     

Evaluation of cefquinome's efficacy in controlling avian colibacillosis and detection of its residues using high performance liquid chromatography (HPLC)

This study aimed to evaluate the efficacy of cefquinome in treatment and controlling of Escherichia coli experimentally infected broiler chickens, in addition of detection of its residues using High performance liquid chromatography (HPLC). In this study, 150 one-day old Cobb broiler chicks were used. On the 14^th day chicks experimentally infected and divided into 3 equal groups (50 each); control group (G1) non-infected, non-treated, (G2) infected with E. coli O₇₈ non treated, (G3) infected with E. coli O₇₈, cefquinome treated. Cefquinome was administrated 5^th day post infection, intramuscularly by a dose of (2 mg/ kg b w.t) for 3 consecutive days. Experimental E. coli infection in broilers induced weakness, loss of appetite, depression, cough and watery diarrhea in addition to a recorded mortality (30%) with reduction in growth performance, erythrogram, total proteins, albumin, antioxidants and haemagglutination inhibition (HI) titers. In addition, a significant increase in feed conversion rate (FCR), leukocytic count, liver enzymes, kidney functions, total globulins, malondialdehyde, nitric oxide and lysozyme activity. Treatment with cefquinome led to decreased mortality rate, improvement in clinical signs, growth performance and modulated most of these altered parameters. Cefquinome's residues was not detected in breast muscles 3^rd day and liver and kidneys 7^th days post treatment. Therefore, it's recommended that cefquinome is a good choice for controlling of colibacillosis in broilers and its withdrawal time 3 days in breast muscles and 7 days in liver and kidney post treatment.     

Axenization and optimization of in vitro growth of clonal cultures of Tetratrichomonas gallinarum and Trichomonas gallinae

A rapid and simple procedure was established to obtain clonal axenic cultures of Tetratrichomonas gallinarum and Trichomonas gallinae and to optimize their in vitro growth conditions. Medium 199 was used for axenization of two genetically different clones of T. gallinarum and T. gallinae. Six different media were used to optimize the growth behaviour of axenically grown parasites: Medium 199, TYM, TYI-S-33, Hollander fluid (HF), Trichomonas vaginalis (TV) and modified TV media. The highest cell yields for both axenic clones of T. gallinarum were obtained in modified TV medium without antibiotics. The maximum numbers of trophozoites of T. gallinae were obtained in an optimized HF medium. This study demonstrated that axenic cultures for T. gallinarum and T. gallinae could be obtained avoiding the migration technique through a V-tube. Following axenization and optimization, both clones of T. gallinarum and T. gallinae could be propagated both aerobically and anaerobically.     

Biosurfactant production by free and alginate entrapped cells of <Emphasis Type="Italic">Pseudomonas fluorescens</Emphasis>

Production of biosurfactant by free and alginate-entrapped cells of Pseudomonas fluorescens Migula 1895-DSMZ was investigated using olive oil as the sole carbon and energy source. Biosurfactant synthesis was followed by measuring surface tension and emulsifying index E24 over 5 days at ambient temperature and at neutral pH. Diffusional limitations in alginate beads affected the kinetics of biosurfactant production when compared to that obtained with free cells culture. Nevertheless, the emulsion stability was improved and fewer by-products interfered with the biosurfactant activity. A decrease in pH down to 5 in the case of immobilized cells was observed during the first 3 days, after which it returned to its initial value. The minimum values of surface tension were 30 and 35 dynes cm⁻¹ achieved after 40 and 72 h with free and immobilized cells, respectively, while the corresponding maximum E24 values were 67 and 62%, respectively. After separation by acetone precipitation, the biosurfactant showed a rhamnolipid-type in nature, and had a good foaming and emulsifying activities. The critical micellar concentration was found to be 290 mg l⁻¹. The biosurfactant also showed good stability during exposure to high temperatures (up to 120 °C for 15 min), to high salinity (10% NaCl) and to a wide range of pH (4–9).     

Ultra morphology of sensilla on the head and mouth parts of the earwig Anisolabis martima (Bonelli) (Dermaptera: Carcinophoridae)

The earwig Anisolabis maritima is a cosmopolitan insect with a worldwide distribution, omnivorous in feeding, eating the eggs of different insects. Recently recorded in Saudi Arabia as a beneficial predator on eggs and newly hatched larvae of the red palm weevil Rhyncophrous ferrugineus, scanning electron microscopy (SEM) observations revealed the presence of different kinds of receptor sensillae occurring on the head and mouth parts of A. maritime. The sensillae are the same, but differ in numbers on both sexes. The head surface bears three subtypes of trichoid sensillae, one type of ceoloconica. Labrum, labium, labial palps and maxillary palps, possess different kinds of sensillae. Three subtypes of trichoid have been identified on the labrum. The labium contained one type of tricoid and basiconic sensillae. There are great numbers and numerous sensillae cheatica differing in length distributed on the maxillary and the labial palps on all segments between other stutter spines. The last terminal segment of maxillary or labial palps bears the greatest number of the sensillae cheatica. Adult A. maritima may be introduced in the future as a beneficial predator of eggs of R. ferrugineus as a tool for integrated pest management.     

The Burden of Non-Communicable Disease in Transition Communities in an Asian Megacity: Baseline Findings from a Cohort Study in Karachi,Pakistan

Background

The demographic transition in South Asia coupled with unplanned urbanization and lifestyle changes are increasing the burden of non-communicable disease (NCD) where infectious diseases are still highly prevalent. The true magnitude and impact of this double burden of disease, although predicted to be immense, is largely unknown due to the absence of recent, population-based longitudinal data. The present study was designed as a unique ‘Framingham-like’ Pakistan cohort with the objective of measuring the prevalence and risk factors for hypertension, obesity, diabetes, coronary artery disease and hepatitis B and C infection in a multi-ethnic, middle to low income population of Karachi, Pakistan.

Methods

We selected two administrative areas from a private charitable hospital’s catchment population for enrolment of a random selection of cohort households in Karachi, Pakistan. A baseline survey measured the prevalence and risk factors for hypertension, obesity, diabetes, coronary artery disease and hepatitis B and C infection.

Results

Six hundred and sixty-seven households were enrolled between March 2010 and August 2011. A majority of households lived in permanent structures (85%) with access to basic utilities (77%) and sanitation facilities (98%) but limited access to clean drinking water (68%). Households had high ownership of communication technologies in the form of cable television (69%) and mobile phones (83%). Risk factors for NCD, such as tobacco use (45%), overweight (20%), abdominal obesity (53%), hypertension (18%), diabetes (8%) and pre-diabetes (40%) were high. At the same time, infectious diseases such as hepatitis B (24%) and hepatitis C (8%) were prevalent in this population.

Conclusion

Our findings highlight the need to monitor risk factors and disease trends through longitudinal research in high-burden transition communities in the context of rapid urbanization and changing lifestyles. They also demonstrate the urgency of public health intervention programs tailored for these transition communities.     

Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3′-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.