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.
Neo vessel formation by angiogenesis is an important event during many pathological conditions including cancer, where it is indispensable for tumor growth and survival. Although, various ...pro‐angiogenic cytokines and soluble factors, secreted by tumor cells, have been reported to promote angiogenesis, recent studies have shown regulatory role of exosomes, secreted by tumor cells in the process of angiogenesis. These exosomes are capable of carrying nucleic acids, proteins, etc., as their cargo. Under the light of these facts and considering the presence of miRNAs, the non‐coding RNAs capable of regulating target gene expression, as one of the major cargos in the exosomes, we investigated, whether exosomes derived from normoxic and hypoxic tumor cell colonies exhibit difference in levels of miR‐23∼27∼24 cluster members and if so, to check the significance of their horizontal transfer on the process of angiogenesis. Results of our study showed that exosomes secreted by hypoxic tumor cell colonies possess significantly higher levels of miR23a and can induce angiogenesis. Further, we have shown that exosomes secreted by cells that ectopically over express miR23a is capable of inducing angiogenesis in different angiogenic model systems such as CAM, in ovo Xenograft and HUVEC models systems. Further, mechanistic analysis revealed that miR23a driven regulation of angiogenesis is brought about by down regulation of SIRT1 in the recipient cells. Collectively, the results presented here suggest that exosomal transfer of miR23a from tumor cell colonies can induce the process of angiogenesis by targeting SIRT1 in the recipient endothelial cells.
Exosomes released from hepatocarcinoma colonies experiencing hypoxia is pro‐angiogenic in nature and the levels of miR‐23a is significantly higher in these exosomes. Further, horizontal transfer of exosomes with higher levels of miR23a can induce angiogenesis by inhibiting SIRT1 in the recipient cells.
Recent studies indicate that horizontal transfer of genetic material can act as a communication tool between heterogenous populations of tumour cells, thus altering the chemosensitivity of tumour ...cells. The present study was designed to check whether the horizontal transfer of miRNAs released by cisplatin resistant (Cp-r) Hepatocarcinoma cells can alter the sensitivity of cervical cancer cells. For this exosomes secreted by cisplatin resistant and cisplatin sensitive HepG2 cells (EXres and EXsen) were isolated and characterised. Cytotoxicity analysis showed that EXres can make Hela cells resistant to cisplatin. Analysis of miR-106a/b levels in EXres and EXsen showed that their levels vary. Mechanistic studies showed that miR-106a/b play an important role in EXsen and EXres mediated change in chemosensitivity of Hela cells to cisplatin. Further SIRT1 was identified as a major target of miR-106a/b using in silico tools and this was proved by experimentation. Also the effect of miR-106a/b in chemosensitivity was seen to be dependent on regulation of SIRT1 by miR-106a/b. In brief, this study brings into light, the SIRT1 dependent mechanism of miR-106a/b mediated regulation of chemosensitivity upon the horizontal transfer from one cell type to another.
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•Characteristics and miRNA profile of exosomes secreted by cells sensitive or resistant to cisplatin differ.•Exosomes secreted by drug resistant cells of one type can confer resistance to another type, against the same drug.•miR-106a and miR106b plays an important role in altering cisplatin sensitivity, when horizontally transferred.•Cisplatin sensitivity mediated by horizontal transport of miR-106a/b is a SIRT-1 dependant mechanism.
The study sought to test whether high-dose statin treatment would result in greater reductions in plaque inflammation than low-dose statins, using fluorodeoxyglucose-positron emission ...tomography/computed tomographic imaging (FDG-PET/CT).
Intensification of statin therapy reduces major cardiovascular events.
Adults with risk factors or with established atherosclerosis, who were not taking high-dose statins (n = 83), were randomized to atorvastatin 10 versus 80 mg in a double-blind, multicenter trial. FDG-PET/CT imaging of the ascending thoracic aorta and carotid arteries was performed at baseline, 4, and 12 weeks after randomization and target-to-background ratio (TBR) of FDG uptake within the artery wall was assessed while blinded to time points and treatment.
Sixty-seven subjects completed the study, providing imaging data for analysis. At 12 weeks, inflammation (TBR) in the index vessel was significantly reduced from baseline with atorvastatin 80 mg (% reduction 95% confidence interval: 14.42% 8.7% to 19.8%; p < 0.001), but not atorvastatin 10 mg (% reduction: 4.2% -2.3% to 10.4%; p > 0.1). Atorvastatin 80 mg resulted in significant additional relative reductions in TBR versus atorvastatin 10 mg (10.6% 2.2% to 18.3%; p = 0.01) at week 12. Reductions from baseline in TBR were seen as early as 4 weeks after randomization with atorvastatin 10 mg (6.4% reduction, p < 0.05) and 80 mg (12.5% reduction, p < 0.001). Changes in TBR did not correlate with lipid profile changes.
Statin therapy produced significant rapid dose-dependent reductions in FDG uptake that may represent changes in atherosclerotic plaque inflammation. FDG-PET imaging may be useful in detecting early treatment effects in patients at risk or with established atherosclerosis.
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-β, 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.
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.
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.
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.
Acquisition of resistance to cisplatin is a major impediment to the success of cisplatin-based combination therapies for cancer. Recent studies indicate that exosomal miRNAs derived from ...drug-resistant tumour cells can confer resistance properties to recipient cells by a horizontal transfer mechanism. Although the role of horizontal transfer of a few miRNAs has been described, little is known about the concerted action of horizontal transfer of miRNAs in conferring cisplatin resistance. The present study was designed to identify the role of miR-643, which is one of the most significantly increased miRNA in exosomes released from cisplatin-resistant Heptocarcinoma cells, in altering the cisplatin resistance properties of recipient cells. Drug-sensitivity assays involving miR-643 revealed that ectopic expression of miR-643 can desensitise the cells towards cisplatin. Furthermore, we identified APOL6 as a major target of miR-643. Further mechanistic studies showed that miR-643 can modulate APOL6 mRNA and protein levels, leading to a reversal of APOL6-mediated apoptosis. Altogether, our results suggest an APOL6-dependent mechanism for miR-643 mediated cisplatin resistance upon the horizontal transfer across cell types.
The Tetradecyltrimethyl ammonium bromide (TTAB) surfactant immobilized carbon paste electrode (TTABMCPE) has been proposed for simultaneous investigation and determination of epinephrine (EP) and ...serotonin (5-HT) in presence of ascorbic acid (AA) by voltammetric techniques, in phosphate buffer solution (PBS) at pH 7.4. The anodic peaks of EP, 5-HT and AA were observed at 198 mV, 363 mV and -17 mV respectively at a scan rate 50 mVs-1. At the TTABMCPE peak currents of all electroactive molecules were increased. It is found that EP and 5-HT could be simultaneously determined with good sensitivity even in the presence of higher concentration of AA. The interference studies showed that the modified electrode had excellent selectivity for the determination of EP in the presence of large excess of AA and 5-HT. The differences of the oxidation peak potentials for EP-AA and EP-5-HT were about 215 and 165 mV, respectively. The voltammetric resolution is large enough to determine AA, EP and 5-HT individually. Detection limit of the modified electrode was found to be 0.12 pM by differential pulse voltammetric technique. The developed method has been applied to the determination of EP in synthetic samples with satisfactory results.
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