Increased IL-6 trans-signaling in depression: focus on the tryptophan catabolite pathway,melatonin and neuroprogression

Depression has been conceptualized as a disorder driven by immuno-inflammatory pathways and oxidative and nitrosative stress. These factors couple to the induction of neuroregulatory tryptophan catabolites via the activation of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). Oxidative damage to neoepitopes increases autoimmune responses, changing the nature of the neural substrate of recurrent depression, which leads to neuroprogression and drives treatment resistance. A number of pro-inflammatory cytokines are linked to these processes. Here, we focus on the role of interleukin (IL)-6 in depression and its associated disorders; we highlight the progress made since the first paper showing increased IL-6 levels was published 20 years ago by Maes and colleagues. When coupled with increased levels of the soluble IL-6 receptor in depression, higher levels of IL-6 may indicate increased IL-6 trans-signaling, whereby IL-6 receptor signaling occurs in cells not normally expressing the IL-6 receptor. It has been suggested that IL-6 is intimately associated with two crucial aspects of depression, as well as central inflammation more broadly. First, the regulation of the local inflammatory response via its interactions with macrophage and glia melatonin production is coupled to local epigenetic modulation via methyl CpG-binding protein 2 (MeCP2). Second, the more systemic regulation of tryptophan availability occurs via the IL-6 induction of IDO. Coupled to its role in the regulation of autoimmune associated T-helper 17 cells and IL-17 production, IL-6 has wide and differential impacts on processes driving depression and a wider range of psychiatric and neurodegenerative conditions.     

Medical Plant Extract Purification from Cadmium(II) Using Modified Thermoplastic Starch and Ion Exchangers

Pure compounds extracted and purified from medical plants are crucial for preparation of the herbal products applied in many countries as drugs for the treatment of diseases all over the world. Such products should be free from toxic heavy metals; therefore, their elimination or removal in all steps of production is very important. Hence, the purpose of this paper was purification of an extract obtained from Dendrobium officinale Kimura et Migo and cadmium removal using thermoplastic starch (S1), modified TPS with poly (butylene succinate); 25% of TPS + 75% PBS (S2); 50% of TPS + 50% PLA (S3); and 50% of TPS + 50% PLA with 5% of hemp fibers (S4), as well as ion exchangers of different types, e.g., Lewatit SP112, Purolite S940, Amberlite IRC747, Amberlite IRC748, Amberlite IRC718, Lewatit TP207, Lewatit TP208, and Purolite S930. This extract is used in cancer treatment in traditional Chinese medicine (TCM). Attenuated total reflectance-Fourier transform infrared spectroscopy, thermogravimetric analysis with differential scanning calorimetry, X-ray powder diffraction, gel permeation chromatography, surface analysis, scanning electron microscopy with energy dispersive X-ray spectroscopy, and point of zero charge analysis were used for sorbent and adsorption process characterization, as well as for explanation of the Cd(II) sorption mechanism.     

Zinc Supplementation Modulates NETs Release and Neutrophils’ Degranulation

Zinc plays an important physiological role in the entire body, especially in the immune system. It is one of the most abundant microelements in our organism and an essential component of enzymes and antibacterial proteins. Zinc levels were reported to be correlated with the intensity of innate immunity responses, especially those triggered by neutrophils. However, as the results are fragmentary, the phenomenon is still not fully understood and requires further research. In this study, we aimed to perform a comprehensive assessment and study the impact of zinc on several basic neutrophils’ functions in various experimental setups. Human and murine neutrophils were preincubated in vitro with zinc, and then phagocytosis, oxidative burst, degranulation and release of neutrophil extracellular traps (NETs) were analyzed. Moreover, a murine model of zinc deficiency and zinc supplementation was introduced in the study and the functions of isolated cells were thoroughly studied. We showed that zinc inhibits NETs release as well as degranulation in both human and murine neutrophils. Our study revealed that zinc decreases NETs release by inhibiting citrullination of histone H3. On the other hand, studies performed in zinc-deficient mice demonstrated that low zinc levels result in increased release of NETs and enhanced neutrophils degranulation. Overall, it was shown that zinc affects neutrophils’ functions in vivo and in vitro. Proper zinc level is necessary to maintain efficient functioning of the innate immune response.     

Glutamate transporters in brain ischemia： to modulate or not？

In this review, we briefly describe glutamate （Glu） metabolism and its specific transports and receptors in the central nervous system （CNS）. Thereafter, we focus on excitatory amino acid transporters, cystine/glutamate antiporters （system xc-） and vesicular glutamate transporters, specifically addressing their location and roles in CNS and the molecular mechanisms underlying the regulation of Glu transporters. We provide evidence from in vitro or in vivo studies concerning alterations in Glu transporter expression in response to hypoxia or ischemia, including limited human data that supports the role of Glu transporters in stroke patients. Moreover, the potential to induce brain tolerance to ischemia through modulation of the expression and/or activities of Glu transporters is also discussed. Finally we present strategies involving the application of ischemic preconditioning and pharmacological agents, eg β-lactam antibiotics, amitriptyline, riluzole and N-acetylcysteine, which result in the significant protection of nervous tissues against ischemia.     

Diagnostic, clinical and laboratory turnaround times in troponin T testing

BACKGROUND: At present, measurements of troponins play a key role in the diagnosis of myocardial infarction. There is a consensus that a turnaround time (TAT) of 1 h or less should be achieved for cardiac marker assays. However, little is known about the real delays between the patient's arrival at the emergency department (ED) and the reporting of the test. METHODS: In the present study, the TATs of a cardiac marker, troponin T (TnT), were analyzed at a central laboratory at Kuopio University Hospital in a population consisting of 215 patients who were admitted to the hospital ED. Four specific time points were recorded: 1) the time of the patient's arrival to the ED, 2) the time of the ordering of the test, 3) the time when blood samples arrived at the laboratory, and 4) the time of completion and reporting of the test. RESULTS: The median diagnostic TAT from patient's arrival to the reporting of the TnT result was 122 min. The clinical median TAT was 46 min and the laboratory median TAT was 69 min. Laboratory TAT consisted of the preanalytical TAT at the ED (median 14 min), pre- and postanalytical TAT in the laboratory (median 40 min), and the analytical TAT (on average 10 min). The laboratory TAT was approximately half of the complete diagnostic TAT. CONCLUSIONS: On the basis of this analysis, we propose new concepts for the TATs in the diagnostic process: diagnostic TAT which consists of clinical and laboratory TAT. The focus should be shifted from the analytical TAT to the diagnostic process as a whole.     

Viscosity Approximation of PDMS Using Weibull Function

The viscosity of a fluid is one of its basic physico-chemical properties. The modelling of this property as a function of temperature has been the subject of intensive studies. The knowledge of how viscosity and temperature variation are related is particularly important for applications that use the intrinsic friction of fluids to dissipate energy, for example viscous torsional vibration dampers using high viscosity poly(dimethylsiloxane) as a damping factor. This article presents a new method for approximating the dynamic viscosity of poly(dimethylsiloxane). It is based on the three-parameter Weibull function that far better reflects the relationship between viscosity and temperature compared with the models used so far. Accurate mapping of dynamic viscosity is vitally important from the point of view of the construction of viscous dampers, as it allows for accurate estimation of their efficiency in the energy dissipation process.     

Interactions between O2 Nanobubbles and the Pulmonary Surfactant in the Presence of Inhalation Medicines

A dispersion of oxygen nanobubbles (O₂-NBs) is an extraordinary gas–liquid colloidal system where spherical gas elements can be considered oxygen transport agents. Its conversion into inhalation aerosol by atomization with the use of nebulizers, while maintaining the properties of the dispersion, gives new opportunities for its applications and may be attractive as a new concept in treating lung diseases. The screening of O₂-NBs interactions with lung fluids is particularly needed in view of an O₂-NBs application as a promising aerosol drug carrier with the additional function of oxygen supplementation. The aim of the presented studies was to investigate the influence of O₂-NBs dispersion combined with the selected inhalation drugs on the surface properties of two types of pulmonary surfactant models (lipid and lipid–protein model). The characteristics of the air–liquid interface were carried out under breathing-like conditions using two selected tensiometer systems: Langmuir–Wilhelmy trough and the oscillating droplet tensiometer. The results indicate that the presence of NBs has a minor effect on the dynamic characteristics of the air–liquid interface, which is the desired effect in the context of a potential use in inhalation therapies.     

Activation of tachykinin system in the pedunculopontine tegmental nucleus suppresses hippocampal theta rhythm in urethane-anesthetized rats

The pedunculopontine tegmental nucleus (PPN) is one of the reticular generators of the hippocampal theta rhythm. The PPN neuronal circuitry related to theta generation involves its cholinergic, GABA-ergic and glutamatergic components. Here we provide data indicating that the PPN tachykinin system may also be a part of this circuitry. In the experimental model of the tail-pinch elicited hippocampal theta in urethane-anesthetized rats (implanted with bilateral recording electrodes in the stratum moleculare of the upper blade of the dentate gyrus and with injection cannula unilaterally inserted into the PPN) it was found that intra-PPN microinjection of Substance P (SP) and [d-Pro2, d-Phe7, d-Trp9]-Substance P (DPDPDT) caused suppression of the theta and enhancement of the delta activity in the hippocampal EEG. Accordingly, there was approximately a 50% (SP)-70% (DPDPDT) decline of the peak power in the theta frequency range and a decrease by 0.4 Hz in the corresponding peak frequency (DPDPDT only) in both hippocampi. The circuitry through which SP exerts its effect in the PPN can be only hypothetical at present. We suggest SP-evoked activation (either direct or indirect through the glutamatergic inputs) of the GABA interneurons which may tonically inhibit PPN outputs to the other theta-relevant structures.