Horizontal transfer of miR-383 sensitise cells to cisplatin by targeting VEGFA-Akt signalling loop.

BACKGROUND: Cellular resistance to cisplatin has been one of the major obstacles in the success of combination therapy for many types of cancers. Emerging evidences suggest that exosomes released by drug resistant tumour cells play significant role in conferring resistance to drug sensitive cells by means of horizontal transfer of genetic materials such as miRNAs. Though exosomal miRNAs have been reported to confer drug resistance, the exact underlying mechanisms are still unclear. METHODS AND RESULTS: In the present study, mature miRNAs secreted differentially by cisplatin resistant and cisplatin sensitive HepG2 cells were profiled and the effect of most significantly lowered miRNA in conferring cisplatin resistance when horizontally transferred, was analysed. we report miR-383 to be present at the lowest levels among the differentially abundant miRNAs expressed in exosomes secreted by cisplatin resistant cells compared to that that of cisplatin sensitive cells. We therefore, checked the effect of ectopic expression of miR-383 in altering cisplatin sensitivity of Hela cells. Drug sensitivity assay and apoptotic assays revealed that miR-383 could sensitise cells to cisplatin by targeting VEGF and its downstream Akt mediated pathway. CONCLUSION: Results presented here provide evidence for the important role of miR-383 in regulating cisplatin sensitivity by modulating VEGF signalling loop upon horizontal transfer across different cell types.

Carbon Quantum Dot-Modified Carbon Paste Electrode-Based Sensor for Selective and Sensitive Determination of Adrenaline.

A carbon quantum dot-based carbon paste electrode was fabricated and used for the determination of adrenaline (AD) at the nanomolar level. This fabricated electrode exhibited tremendous electrocatalytic activity for the oxidation of adrenaline in supporting electrolyte (PBS of pH 7.4). Scan rate variation studies with the modified electrode revealed that the overall electrode process was controlled by a diffusion process. A lower detection limit of 6 nM was achieved by chronoamperometry. Interference by biological molecules such as serotonin (5-HT) and ascorbic acid (AA) in the electrochemical oxidation of AD on the fabricated electrode was tested. It was observed that with the modified electrode, the selective determination of AD was possible. Further, with the fabricated electrode, simultaneous analysis of AA, AD, and 5-HT was performed, and it was observed that the overlapped peaks of these analytes on the naked electrode were well resolved into three peaks on the modified electrode. Along with decent sensitivity and selectivity, the electrode also showed higher stability and antifouling nature. The real-time application of the projected scheme was proven by employing the said electrode for adrenaline in adrenaline bitartrate injections.

Role of Sirtuins in Tumor Angiogenesis.

Generally, changes in the metabolic status of cells under conditions like hypoxia and accumulation of lactate can be sensed by various sensing mechanisms, leading to modulation of a number of signal transduction pathways and transcription factors. Several of the proangiogenic cytokines like VEGF, FGF, PDGF, TGF-ß, Ang-2, ILs, etc. are secreted by cancer cells, under hypoxic microenvironment. These cytokines bind to their receptors on the endothelial cells and activates a number of signaling pathways including Akt/PIP3, Src, p38/MAPK, Smad2/3, etc., which ultimately results in the proliferation and migration of endothelial cells. Transcription factors that are activated in response to the metabolic status of tumors include HIFs, NF-κb, p53, El-2, and FOXO. Many of these transcription factors has been reported to be regulated by a class of histone deacetylase called sirtuins. Sirtuins are NAD+ dependent histone deacetylases that play pivotal role in the regulation of tumor cell metabolism, proliferation, migration and angiogenesis. The major function of sirtuins include, deacetylation of histones as well as some non-histone proteins like NF-κB, FOXOs, PPAR⋎, PGC1-α, enzymes like acetyl coenzymeA and structural proteins like α tubulin. In the cell, sirtuins are generally considered as the redox sensors and their activities are dependent on the metabolic status of the cell. Understanding the intricate regulatory mechanisms adopted by sirtuins, is crucial in devising effective therapeutic strategies against angiogenesis, metastasis and tumor progression. Keeping this in mind, the present review focuses on the role of sirtuins in the process of tumor angiogenesis and the regulatory mechanisms employed by them.

Electrochemical Determination of Adrenaline Using MXene/Graphite Composite Paste Electrodes.

MXene/graphite composite paste electrode (MXene/GCPE)-based electrochemical sensor has been fabricated for the detection of adrenaline. The electrode exhibits a sensitive response to adrenaline in phosphate buffer solution of pH 7.4, and its catalytic activity is much higher than that of the bare graphite paste electrode. The electron-transfer reaction of MXene/GCPE is a diffusion controlled process. The graph of concentration of adrenaline with the peak current exhibits two linearities, one in the lower and other in the higher concentration range with a detection limit of 9.5 nM. The simultaneous analyses of adrenaline, ascorbic acid, and serotonin reveal that the fabricated electrode could separate the overlapped cyclic voltammetric peaks of these ternary mixtures. This electrode has been further employed in the detection of adrenaline in pharmaceutical samples with 99.2-100.8% recoveries.

Angiogenic Profiling of Synthesized Carbon Quantum Dots.

A simple method was employed for the synthesis of green luminescent carbon quantum dots (CQDs) from styrene soot. The CQDs were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared, and Raman spectroscopy. The prepared carbon quantum dots did not show cellular toxicity and could successfully be used for labeling cells. We also evaluated the effects of carbon quantum dots on the process of angiogenesis. Results of a chorioallantoic membrane (CAM) assay revealed the significant decrease in the density of branched vessels after their treatment with CQDs. Further application of CQDs significantly downregulated the expression levels of pro-angiogenic growth factors like VEGF and FGF. Expression of VEGFR2 and levels of hemoglobin were also significantly lower in CAMs treated with CQDs, indicating that the CQDs inhibit angiogenesis. Data presented here also show that CQDs can selectively target cancer cells and therefore hold potential in the field of cancer therapy.