STEAP4 and HIF-1α gene expressions in visceral and subcutaneous adipose tissue of the morbidly obese patients

Aim and backgroundObesity is a multifactorial disease in which environmental and genetic factors play an integrated role. Determining such target genes will help to elucidate the mechanisms underlying complex diseases such as obesity and diabetes which are usually seen together. Present study investigates the expression levels of STEAP4 and HIF-1α in visceral and subcutaneous adipose tissue.Patients and methods30(6 M) morbidly obese patients undergoing bariatric surgery were included in the study. The patients were grouped according to the BMI as Group I (BMI <50 kg/m²) and Group II (BMI ≥50 kg/m²). Samples from visceral (omentum) and subcutaneous adipose tissues were obtained from each patient and real-time PCR (qPCR) was carried out for STEAP4 and HIF-1α gene expressions. Correlations between expression levels and clinical parameters were analyzed.ResultsMean age of the patients recruited to the study was 37.4 (18–64) years. Mean BMI was 46 (36–60) kg/m². STEAP4 expression in visceral adipose tissue was significantly higher than subcutaneous tissue. Visceral STEAP4 expression was also found to be reduced with increased BMI. It was also lower in patients with HbA₁C over 6. Furthermore, expression of subcutaneous and visceral HIF-1α was significantly higher in Group II. There was a significant correlation between BMI, glycosylated hemoglobin, STEAP4 and HIF-1α gene expression.ConclusionsObesity and related disease are linked with the fact that there is a low grade inflammation in the adipose tissue of the obese individuals. Counter-regulatory processes such as STEAP4 protein family are overwhelmed by the proinflammatory stimuli. HIF-1α expression is increased due to tissue hypoxia and pro-inflammatory stimuli in the obese individuals, which results in increased visceral STEAP4 expressions.     

Autoimmune bone marrow environment severely inhibits B cell development by inducing extensive cell death and inhibiting proliferation

Plasmacytoid dendritic cell (PDC) is a Th2-type dendritic cell precursor. It is an important professional effector cell characterized by its capacities to produce large amount of alpha interferon and to differentiate into dendritic cell. PDCs are scarce in normal condition. They circulate in the blood as veiled cells and enter the lymph node and mucosal site in response to immune stimulation. Besides the recent and wide-open field of the implication of PDCs in inflammatory diseases and in the microenvironment of solid or lymphoid tumours it has also been observed that PDCs can also be tumoral cells. In this paper, the authors present the different tumours thought to be originating from tumoral PDCs. To date, two kinds of tumoral conditions are recognized: the so-called PDCs proliferations in patients with myeloid disorders and the blastic plasmacytoid dendritic cell neoplasm. These two entities are exposed and discussed.     

Devitalisierimg Ron Lebenden Pulpen Durch Diathermic

Zusammenfassung

Die Koagulierung der vitalen Pulpa mittels Diathermie wird, im Vergleich zu der Arsenik-Devitalisation und der Vital-Exstirpation, als günstig hervorgehoben. Die Vorteile sind: Koagulation, Exstirpation und Wurzelfüllung können in einer Sitzung stattfinden. Ausser Zeitgewinn, bedeutet dies eine Verminderung der Infektionsgefahr von aussen. Wir erhalten eine reine, aseptische Wundfläche, welche leicht zu heilen ist. Eest-Pulpitiden und Nachblutungen sind nicht eingetroffen. Klinischrontgenologische Untersuchung von 116 Fällen mit einer Kontrollzeit von 4 bis 40 Monaten, zeigt, dass die Wurzelfüllung in 97% der Falle als gelungen zu betrachten ist. Die Behandlung wurde unter Anästhesie ausgeführt. Die anderweitig vermuteten Nachteile, u. a. die Gefahr fiir Verbrennung, wurden nicht von der Untersuchung bestatigt.     

Local and systemic tolerability of a 2′O-methoxyethyl antisense oligonucleotide targeting interleukin-4 receptor-α delivery by inhalation in mouse and monkey

Abstract

Antisense oligonucleotides (ASOs) bind and facilitate degradation of RNA and inhibit protein expression in pathways not easily targeted with small molecules or antibodies. Interleukin (IL)-4 and IL-13 potentiate signaling through the shared IL-4 receptor-α (IL-4Rα) subunit of their receptors. ASO targeting of IL-4Rα mRNA in a mouse model of asthma led to attenuation of airway hyperactivity, demonstrating potential benefit in asthma patients. This study focused on tolerability of inhaled IL-4Rα-targeting ASOs. Toxicity studies were performed with mouse- (ISIS 23189) and human-specific (ISIS 369645) sequences administered by inhalation. Four week (monkey) or 13 week (mouse) repeat doses at levels of up to 15?mg/kg/exposure (exp) and 50?mg/kg/exp, respectively, demonstrated dose-dependent effects limited to increases in macrophage size and number in lung and tracheobronchial lymph nodes. The changes were largely non-specific, reflecting adaptive responses that occur during active exposure and deposition of ASO and other material in the lung. Reversibility was observed at a rate consistent with the kinetics of tissue clearance of ASO. Systemic bioavailability was minimal, and no systemic toxicity was observed at exposure levels appreciably above pharmacological doses and doses proposed for clinical trials.     

Inhibition of Staphylococcus Aureus Mediated by Extracts from Iranian Plants

In order to find new antibacterial agents effective against Staphylococcus aureus, ethanolic extracts of 10 plants were tested. S. aureus (489 samples) were isolated either from healthy carriers (nose and throat) or clinical samples. Out of 489 isolates tested, 98.6% were sensitive to trimethoprim-sulfamethoxazole which was used as the reference antibiotic. From the plant extracts screened for antibacterial activity, Myrtus communis L. (leaves) had the greatest activity, inhibiting the growth of 99% of the isolates. Glycyrrhiza glabra L., Eucalyptus globolus Labill and Menta viridis L., were also active against the isolates inhibiting the growth of 90, 59.5 and 48.7% of the isolates, respectively. All of these extracts were active against the reference strains of S. aureus tested. Saturia hortensis L., Teucrium polium L., and Achillea santolina L., had very little antibacterial activity, while Trigonella foenum graecum L., Echium amoenum Fisch & Mey (flowers) and Juglans regia L. (leaves), had no antibacterial activity against the bacterial isolates.     

Lack of BCL-2 confers interferon-alpha sensitivity to B-cell lymphomas

Hairy cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder with pathological manifestations usually including splenomegaly and panctopenia. Interferons (IFNs), specifically of the α subtypes have shown a significant anti-tumor effect in HCL patients, with improvement of hematological parameters within the first few months of treatment. However, the therapeutic effect of IFN-α is still rather limited. The mechanisms responsible for the beneficial action of IFN-α in HCL patients are unclear. A continuous line of cells (Eskol) from a patient diagnosed with HCL was established and shown to have several properties of HCL. Even though, Eskol cells are very resistant to anti-proliferative activity of IFN-α, Daudi cells, another human B-cell-derived cell line, are very sensitive to anti-proliferative activity of IFN-α and are commonly used as a model cell to test anti-proliferative effect of IFN-α. To understand the molecular reason(s) behind the observed obvious differences to IFN sensitivity of above cells, we have analyzed the expression levels of BCL2, caspase-1, Laminin and PARP in these cells. We found that Daudi cells do not express BCL2 at all, and probably because of that, these cells have constantly cleaved, and probably activated form of caspase-1. However, when we overexpresed BCL2 in these cells, they lost processed form of caspase-1 and became resistant to anti-proliferative activity of IFN-α. These results let us to suggest that IFN-α sensitivity of B-cell lymphomas, once again, depends on the presence or absence of BCL2.     

Positive AMPA receptor modulation in the treatment of neuropsychiatric disorders: A long and winding road

Glutamatergic transmission is widely implicated in neuropsychiatric disorders, and the discovery that ketamine elicits rapid-acting antidepressant effects by modulating α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) signaling has spurred a resurgence of interest in the field. This review explores agents in various stages of development for neuropsychiatric disorders that positively modulate AMPARs, both directly and indirectly. Despite promising preclinical research, few direct and indirect AMPAR positive modulators have progressed past early clinical development. Challenges such as low potency have created barriers to effective implementation. Nevertheless, the functional complexity of AMPARs sets them apart from other drug targets and allows for specificity in drug discovery. Additional effective treatments for neuropsychiatric disorders that work through positive AMPAR modulation may eventually be developed.