Hypothermia Alleviates Reductive Stress,a Root Cause of Ischemia Reperfusion Injury

Ischemia reperfusion injury is common in transplantation. Previous studies have shown that cooling can protect against hypoxic injury. To date, the protective effects of hypothermia have been largely associated with metabolic suppression. Since kidney transplantation is one of the most common organ transplant surgeries, we used human-derived renal proximal tubular cells (HKC8 cell line) as a model of normal renal cells. We performed a temperature titration curve from 37 °C to 22 °C and evaluated cellular respiration and molecular mechanisms that can counteract the build-up of reducing equivalents in hypoxic conditions. We show that the protective effects of hypothermia are likely to stem both from metabolic suppression (inhibitory component) and augmentation of stress tolerance (activating component), with the highest overlap between activating and suppressing mechanisms emerging in the window of mild hypothermia (32 °C). Hypothermia decreased hypoxia-induced rise in the extracellular lactate:pyruvate ratio, increased ATP/ADP ratio and mitochondrial content, normalized lipid content, and improved the recovery of respiration after anoxia. Importantly, it was observed that in contrast to mild hypothermia, moderate and deep hypothermia interfere with HIF1 (hypoxia inducible factor 1)-dependent HRE (hypoxia response element) induction in hypoxia. This work also demonstrates that hypothermia alleviates reductive stress, a conceptually novel and largely overlooked phenomenon at the root of ischemia reperfusion injury.     

Upgrading of wakefield browncoal from south Australia

A sample of Wakefield browncoal, which is of very poor quality, was subjected to various treatments to improve the calorific value and remove contaminants. The best coal product, with a calorific value of 30 MJ/kg, was obtained by hydrothermal upgrading: 91% of the combustibles present in the feedstock were concentrated in 34% of the original weight. Moreover, an amount of liquid products was generated in a yield of up to 10 wt% on dry intake. Via a Fleissner treatment ca. 70% of the inherent moisture was removed as a liquid, leaving a product whose calorific value is expected to be almost 20 MJ/kg. Via carbonization smokeless fuels can be produced with a heating value of ca. 28 MJ/kg and yields of 50–60%, depending on the temperature. From this particular browncoal, most of the silica fraction of the mineral matter was extracted by rinsing with water, thus reducing the ash content by 50% and the ash fusion temperature by almost 200°C. By combined thermal upgrading and washing, most of the contaminants, i.e., sodium and chlorine, and half of the amount of oxygen and sulphur were removed. On the basis of experiments with micro-gasification test equipment, Wakefield browncoal and its upgraded product seem attractive feedstocks for gasification from a reactivity point of view. The lowering of the ash fusion temperature as observed in washed products is important for the reduction of the reactor outlet temperature when gasifying under slagging conditions, which has a favourable effect on the thermal efficiency.     

The Expression Pattern of Genes Related to Melanogenesis and Endogenous Opioids in Psoriasis

The melanocortin system is a major regulator of stress responses in the skin and is responsible for the induction of melanin synthesis through activation of melanogenesis enzymes. The expression of both melanocortin system genes and melanogenesis enzyme genes is altered in psoriasis, and the focus here was on twelve genes related to the signal transduction between them. Additionally, five endogenous opioid system genes that are involved in cutaneous inflammation were examined. Quantitative real-time-PCR was utilized to measure mRNA expression in punch biopsies from lesional and non-lesional skin of psoriasis patients and from the skin of healthy control subjects. Most of the genes related to melanogenesis were down-regulated in patients (CREB1, MITF, LEF1, USF1, MAPK14, ICAM1, PIK3CB, RPS6KB1, KIT, and ATRN). Conversely, an up-regulation occurred in the case of opioids (PENK, PDYN, and PNOC). The suppression of genes related to melanogenesis is in agreement with the reported reduction in pigmentation signaling in psoriatic skin and potentially results from the pro-inflammatory environment. The increase in endogenous opioids can be associated with their involvement in inflammatory dysregulation in psoriasis.