The microRNA Expression Profile in Donation after Cardiac Death (DCD) Livers and Its Ability to Identify Primary Non Function

Donation after cardiac death (DCD) livers are marginal organs for transplant and their use is associated with a higher risk of primary non function (PNF) or early graft dysfunction (EGD). The aim was to determine if microRNA (miRNA) was able to discriminate between DCD livers of varying clinical outcome. DCD groups were categorized as PNF retransplanted within a week (n=7), good functional outcome (n=7) peak aspartate transaminase (AST) ≤ 1000 IU/L and EGD (n=9) peak AST ≥ 2500 IU/L. miRNA was extracted from archival formalin fixed post-perfusion tru-cut liver biopsies. High throughput expression analysis was performed using miRNA arrays. Bioinformatics for expression data analysis was performed and validated with real time quantitative PCR (RT-qPCR). The function of miRNA of interest was investigated using computational biology prediction algorithms. From the array analysis 16 miRNAs were identified as significantly different (p<0.05). On RT-qPCR miR-155 and miR-940 had the highest expression across all three DCD clinical groups. Only one miRNA, miR-22, was validated with marginal significance, to have differential expression between the three groups (p=0.049). From computational biology miR-22 was predicted to affect signalling pathways that impact protein turnover, metabolism and apoptosis/cell cycle. In conclusion, microRNA expression patterns have a low diagnostic potential clinically in discriminating DCD liver quality and outcome.     

Graphene oxide-methylene blue nanocomposite in photodynamic therapy of human breast cancer

The interaction of methylene blue (MB) as a photosensitizer with graphene oxide nano-sheets (GO) was examined in aqueous solution using UV-vis spectrophotometric techniques. MB–GO composites were prepared by mixing the solutions of GO nano-sheets and methylene blue due to interacting of the cationic methylene blue photosensitizer via electrostatic and π–π stacking or hydrophobic cooperative interactions. The cell killing potential of nanocomposite was examined on the MDA-MB-231 breast cancer cells in the absence and presence of red LED irradiation. The results demonstrated that the MB-GO nanocomposite has good performance in photodynamic therapy (PDT) during red LED irradiation. The cytotoxicity of nanocomposite caused reducing cell viability up to 20%. These effects would be due to the nano size structure of composite that could lead to effective cellular penetration. Also the significant difference has seen in lower concentrations of MB and MB-GO nanocomposite. The results show more than 40% increases in cell killing potential in lower concentrations of nanocomposite by using 2.5 μg/mL of each compound. The ratio of GO/MB can affect the interaction and higher ratios of graphene oxide (GO/MB > 1) can induce dimerization of MB. In lower concentrations and ratios of (GO/MB < 1) the free MB concentration increases and the electron shuttling effect of GO in photo activity decreases – which could affect the photocatalytic yield in PDT. The cell viability measurements confirm these effects on cancer cell killing potential of nanocomposite. According to microscopic and PDT assay results, the nanocomposite distribution and diffusion in cells enhanced the photochemical reaction yield in photodynamic therapy of MDA-MB-231 breast cancer cell line.     

Taurine attenuates valproic acid-induced hepatotoxicity via modulation of RIPK1/RIPK3/MLKL-mediated necroptosis signaling in mice

Molecular Biology Reports - Valproic acid (VPA) is known as a common drug in seizure and bipolar disorders treatment. Hepatotoxicity is the most important complication of VPA. Taurine (Tau), an...     

Low-dose photodynamic therapy effect on closure of scratch wounds of normal and diabetic fibroblast cells: An in vitro study

Chronic wounds such as diabetic ulcers are a serious public health problem. Extensive research is needed to find new alternatives for wound treatment. Photodynamic therapy (PDT) is a non-invasive method, which has been studied for several decades to treat cancer, infections, and other diseases. PDT involves the administration of a photosensitizer compound followed by irradiation with using light at specific wavelength to produce reactive oxygen species (ROS) using molecular oxygen. It is possible that low dose photodynamic therapy (LDPDT) could improve wound healing and stimulates the cell repair process. This study we explored the effect of LDPDT on wound healing in vitro using normal and diabetic cellular wound models. The effects of different concentrations of 5-ALA and different energy densities (dark or light) on the cell viability of human fibroblast cells were studied using the MTT assay. After ascertaining the optimum parameters, a scratch wound assay was performed on both normal and diabetic cells and then cells treated with 1 and 5 μg/mL of 5-ALA at 1 J/cm² energy density. ROS production and morphological alteration of the cells were studied. The mortality of normal fibroblast cells increased with increasing 5-ALA concentration and also increasing energy density (up to 3 J/cm²). However, in diabetic cells, the mortality rate did not decrease. Diabetic cells showed increased migration and closure of the scratch compared to normal cells under similar conditions. A low concentration of 5-ALA (5 μg/mL) and low energy density of 1 J/cm² in both normal and diabetic cells gave a small increase in ROS levels compared to controls. This may explain the positive effects of LDPDT on wound healing. The findings of this study suggest that LDPDT may have a potential effect on the wound healing of diabetic wounds.