Discovery and target identification of small molecule autophagy inhibitors See

Pharmacologically active substances have been applied in medicine for at least 5300 years.Ever since, mankind has tried to enlarge the assortment of bio-active substances, in order to fight diseases and ultimately maintain health and quality of life. For thousands of years, but especially in the last century, drug discovery has been the scientific key driver for the progression of medicine. One process that attracts notable attention due to its high potential for the development of new drugs...

User-aware performance evaluation and optimization of parallel job schedulers See

Die Dissertation User-Aware Performance Evaluation and Optimization of Parallel Job Schedulers beschäftigt sich mit der realitätsnahen, dynamischen Simulation und Optimierung von Lastsituationen in parallelen Rechensystemen unter Berücksichtigung von Feedback-Effekten zwischen Performance und Nutzerverhalten. Die Besonderheit solcher Systeme liegt in der geteilten Nutzung durch mehrere Anwender, was zu einer Einschr änkung der Verfügbarkeit von Ressourcen führt. Sollten nicht alle Rechenanfra...

Knock off and on: a novel approach to autophagy modulation See

Random finite set filters for superpositional sensors See

The multi–object filtering problem is a generalization of the well–known single– object filtering problem. In essence, multi–object filtering is concerned with the joint estimation of the unknown and time–varying number of objects and the state of each of these objects. The filtering problem becomes particular challenging when the number of objects cannot be inferred from the collected observations and when no association between an observation and an object is possible. A rather new and pr...

Identification and biological characterization of indoline-based autophagy inhibitors See

Autophagy is a vital catabolic process involved in the degradation of cellular components, which plays an important role in cancer and neurodegenerative disorders. Due to their high complexity, the pathways regulating autophagy have not been fully elucidated. The development of specific autophagy modulators and the identification of their cellular targets can provide valuable insight into the regulation of this process and, ultimately, its role in disease. Herein, a potent inhibitor of star...

Schisandrae Fructus ethanol extract ameliorates inflammatory responses and articular cartilage damage in monosodium iodoacetate-induced osteoarthritis in rats See

Schisandrae Fructus, the fruit of Schisandra chinensis (Turcz.) Baill., is widely used in traditional medicine for the treatment of a number of chronic diseases. Although, Schisandrae Fructus was recently reported to attenuate the interleukin (IL)-1β-induced inflammatory response in chondrocytes in vitro, its protective and therapeutic potential against osteoarthritis (OA) in an animal model remains unclear. Therefore, we investigated the effects of the ethanol extract of Schisandrae Fructus ...

Effects of symbiotic and vitamin E supplementation on blood pressure, nitric oxide and inflammatory factors in non-alcoholic fatty liver disease See

Non-alcoholic fatty liver disease (NAFLD) has been suggested to be well correlated with altered blood pressure. This study was conducted to determine the effects of symbiotic and vitamin E supplementation on blood pressure and inflammatory indices of patients with NAFLD. This randomized, double-blind, placebo-controlled trial was performed among 60 NAFLD patients aged 25 to 64 years old. Participants were randomly divided into four groups to receive a 400 IU alpha-tocopherol and 2 ×...

Seroepidemiological study of Toxoplasma gondii infection in a population of Iranian epileptic patients See

Epilepsy is one of the most common neurologic disorders. Underlying cause of epilepsy is unknown in 60 % of the patients. Toxoplasma gondii is an intracellular parasite which is capable of forming tissue cysts in brain of chronically infected hosts including humans. Some epidemiological studies suggested an association between tox- oplasmosis and acquisition of epilepsy. In this study we determined seroprevalence of latent Toxoplasma infection in a population of Iranian epileptic patien...

Evaluating the relationship of blood pressure, plasma angiotensin peptides and aldosterone with cognitive functions in patients with hypertension See

Renin Angiotensin Aldosterone System (RAAS) plays an important role in the development of hypertension. On the other hand, hypertension is a well-known and independent risk factor for cognitive impairment. The aim of the present study was to evaluate the relationship of blood pressure control, plasma angiotensin peptides and aldoste- rone with cognitive functions. Forty-one patients who were under treatment with the same antihypertensive med- ications for at least three months were ...

Lungs deposition and pharmacokinetic study of submicron budesonide particles in Wistar rats intended for immediate effect in asthma See

The purpose of the present investigation was to study the aerosolization, lungs deposition and pharmacokinetic study of inhalable submicron particles of budesonide in male Wistar rats. Submicron particles were prepared by antisolvent nanoprecipitation method and freeze-dried to obtain free flowing powder. The freeze-drying process yielded dry powder with desirable aerodynamic properties for inhalation therapy. An in-house model inhaler was designed to deliver medicine to lungs, opti...

Paradoxical effect of minocycline on established neuropathic pain in rat See

Neuropathic pain occurs after peripheral nerve damage, inflammation or infection. In this situation, microglial cells become activated and play a key role in producing pain. Minocycline (microglia inhibitor), was reported to reduce pain when used preventively. However, it seems that, when used after nerve injury, results in its pain reducing effects are different. In this regard, to assess the pain reducing differences of minocycline, neuropathic pain was induced by the ligation of ...

Preparation and characterization of beta-glucan particles containing a payload of nanoembedded rifabutin for enhanced targeted delivery to macrophages See

β-glucan particles (GP) are polymeric carbohydrates, mainly found as components of cell wall fungi, yeast, bacteria and also in cereals such as barley and oat, and have been recently shown to have application in macrophagetargeted drug delivery. The aim of this study was to prepare and characterize GP containing a large payload of Rifabutin (RB), an anti-tuberculosis drug effective against MDR-TB at lower MIC than Rifampicin. GP were prepared from yeast cells by acidic and alkaline extraction...

High level of miR-196b at newly diagnosed pediatric acute myeloid leukemia predicts a poor outcome See

Differential expression of microRNAs (miRNAs) has been implicated in leukemogenesis. We investigate the ex- pression pattern of miR-196b. Using quantitative real-time PCR (qRT-PCR), we detected the expression of miR- 196b and its correlated genes (SMC1A/MLH1) in initial pediatric AML. A significant association was observed between overexpression of miR-196b and inferior overall survival of pediatric AML (Log Rank P<0.0001). AML M4/5 subtype, high white blood ...

Chemical composition and biological activities of Salvia officinalis essential oil from Tunisia See

The aim of this study is to evaluate the chemical composition, antioxidant, antimicrobial, insecticidal and allelopa- thic activities of Tunisia Salvia officinalis essential oil (SoEO). The SoEO was characterized by the presence of 49 components with camphor (25.14 %), α-thujone (18.83 %), 1,8-cineole (14.14 %), viridiflorol (7.98 %), β-thu- jone (4.46 %) and β-caryophyllene (3.30 %) as the major components, determined by gas chromatography-mass spectrometry. The level of antioxidan...

Study of the cytotoxic effects of 2,5-diaziridinyl-3,6-dimethyl-1,4-benzoquinone (MeDZQ) in mouse hepatoma cells See

A number of quinones have been shown to be efficient anticancer agents. However, some mechanisms of their action, in particular cell signaling are not well understood. The aim of this study was to partly fill this gap by characterizing the mode of cytotoxicity of 2,5-diaziridinyl-3,6-dimethyl-1,4-benzoquinone (MeDZQ) in malignant mouse hepatoma cells (MH-22A) with regard to the expression and activation of main molecules in MAPK cell signaling pathway. The study revealed unequal roles of MAP ...

Effect of melatonin supplemented at the light or dark period on recovery of sciatic nerve injury in rats See

Peripheral nerve injuries can cause disabilities, social or economic problems. Melatonin, the secretory product of the pineal gland has antioxidant and anti-inflammatory actions. The aim of the present study was to investigate the effect of melatonin on the recovery of sciatic nerve after injury, comparing its effect when given in the light or the dark periods. Forty adult male Albino rats were allocated into four groups: control, nerve injury, nerve injury + melatonin given at light and nerv...

Identifizierung und Charakterisierung neurotropher Naturstoffderivate und kovalenter Kinesininhibitoren See

Die Neugestaltung des neuronalen Netzwerkes ist essentiell für die Wiederherstellung der physiologischen Funktionen nach neuronaler Schädigung, weshalb die Erforschung neuartiger Therapeutika mit neurotrophen Eigenschaften von großer Bedeutung ist. In dieser Arbeit wurde ein Testsystem zur Identifizierung neuromodulatorischer Substanzen in der Neuroblastomzelllinie SH-SY5Y entwickelt. Durch Anwendung dieses Testsystems konnten neurotrophe Verbindungen auf Basis der Naturstoffe Militarinon A u...

WNT1-inducible signaling pathway protein-1 (WISP1), a novel critical protein in hepatotoxic liver injury See

Zellgängige Peptide zur Inhibition des Wnt/β-Catenin Signalweges See

Der Wnt/β-Catenin Signalweg kontrolliert fundamentale Prozesse der Embryonalentwicklung sowie die Homöostase im adulten Gewebe. Fehlregulation durch konstitutive Aktivierung resultiert in übermäßiger Proliferation und fördert die Entstehung von Krebs. Die Inhibition des Signalweges ist sehr anspruchsvoll, da dieser durch Protein-Protein-Interaktionen (PPIs) reguliert wird, die nur schwer mit niedermolekularen Verbindungen moduliert werden können. Peptide weisen gute Bindungseigenschaften für ...