Dissecting the roles of exosomal cancer-associated fibroblasts-derived non-coding RNAs in tumor progression: A complete guide.

Cancer-associated fibroblasts are the most important cellular component of the tumor microenvironment, controlling cancer progression and therapeutic response. These cells in the tumor microenvironment regulate tumor progression and development as oncogenic or tumor suppressor agents. However, the mechanisms by which CAFs communicate with cancer cells remain to investigate. Here, we review evidence that extracellular vesicles, particularly exosomes, serve as vehicles for the intercellular transfer of bioactive cargos, notably microRNAs and long non-coding RNAs, from CAFs to cancer cells. We try to highlight molecular pathways of non-coding RNAs and the interaction among these molecules. Together, these findings elucidate a critical exosome-based communication axis by which CAFs create mostly a supportive pro-tumorigenic microenvironment and highlight therapeutic opportunities for disrupting this intercellular crosstalk.

The effect of magnesium sulfate on maternal serum electrolytes and parathyroid hormone in pre-eclampsia.

OBJECTIVE: To evaluate possible interactions of magnesium sulfate-the drug of choice in the management of pre-eclampsia/eclampsia-in response to a few case reports that revealed maternal electrolyte disturbances, especially symptomatic changes, following magnesium sulfate administration in pre-eclampsia. METHODS: Prospectively, women with pre-eclampsia were given 4 g of intravenous magnesium sulfate followed by a 2 g/h infusion up to 24 h after delivery. Sequential blood samples were drawn from each patient and used to measure the serum levels of sodium, potassium, calcium, phosphorus, magnesium, and parathyroid hormone. RESULTS: A total of 30 pregnant women with pre-eclampsia were evaluated. They were aged between 20 and 41 years with median gestational age of 37.6 (interquartile range 35.4-38.9) weeks. Only five patients reached the therapeutic window of magnesium in at least one of our measuring intervals during magnesium sulfate infusion. Plasma magnesium concentrations increased significantly during magnesium sulfate administration and dropped during the next 12 and 24 h after infusion discontinuation (P < 0.05). Fifteen of 30 (50%) patients developed asymptomatic hypocalcemia, mainly at hour 24 of infusion. Negative moderate correlations were detected between the calcium and magnesium concentrations at 12 and 24 hours of infusion (ρ = -0.390, P = 0.044 and ρ = 0.315, P = 0.096, respectively). None of the patients with hypocalcemia reached the therapeutic level of magnesium or experienced parallel hyperphosphatemia. Eleven of 30 (36.6%) patients developed hyperphosphatemia mainly at 2 and 12 h of magnesium sulfate infusion. CONCLUSIONS: Our study implies that magnesium sulfate could cause hypermagnesemia-induced hypocalcemia in women with pre-eclampsia, independent from parathyroid hormone. The negative correlations between calcium and magnesium concentrations could be indicative of dose-dependent associations between serum magnesium level and degree of hypocalcemia in our study.

Unexpected peaks in tandem mass spectra due to reaction of product ions with residual water in mass spectrometer collision cells.

RATIONALE: Certain product ions in electrospray ionization tandem mass spectrometry are found to react with residual water in the collision cell. This reaction often leads to the formation of ions that cannot be formed directly from the precursor ions, and this complicates the mass spectra and may distort MRM (multiple reaction monitoring) results. METHODS: Various drugs, pesticides, metabolites, and other compounds were dissolved in acetonitrile/water/formic acid and studied by electrospray ionization mass spectrometry to record their MS(2) and MS(n) spectra in several mass spectrometers (QqQ, QTOF, IT, and Orbitrap HCD). Certain product ions were found to react with residual water in collision cells. The reaction was confirmed by MS(n) studies and the rate of reaction was determined in the IT instrument using zero collision energy and variable activation times. RESULTS: Examples of product ions reacting with water include phenyl and certain substituted phenyl cations, benzoyl-type cations formed from protonated folic acid and similar compounds by loss of the glutamate moiety, product ions formed from protonated cyclic siloxanes by loss of methane, product ions formed from organic phosphates, and certain negative ions. The reactions of product ions with residual water varied greatly in their rate constant and in the extent of reaction (due to isomerization). CONCLUSIONS: Various types of product ions react with residual water in mass spectrometer collision cells. As a result, tandem mass spectra may contain unexplained peaks and MRM results may be distorted by the occurrence of such reactions. These often unavoidable reactions must be taken into account when annotating peaks in tandem mass spectra and when interpreting MRM results. Published in 2014. This article is a U.S. Government work and is in the public domain in the USA.