Backgrounds/aims Mesenchymal stromal cell-derived exosomes (MSC-EXs) could exert protective effects on recipient cells by transferring the contained microRNAs (miRs), and miR-132-3p is one of angiogenic miRs. However, whether the combination of MSC-EXs and miR-132-3p has better effects in ischemic cerebrovascular disease remains unknown. Methods Mouse MSCs transfected with scrambler control or miR-132-3p mimics were used to generate MSC-EXs and miR-132-3p-overexpressed MSC-EXs (MSC-EXsmiR-132-3p). The effects of EXs on hypoxia/reoxygenation (H/R)-injured ECs in ROS generation, apoptosis, and barrier function were analyzed. The levels of RASA1, Ras, phosphorylations of PI3K, Akt and endothelial nitric oxide synthesis (eNOS), and tight junction proteins (Claudin-5 and ZO-1) were measured. Ras and PI3K inhibitors were used for pathway analysis. In transient middle cerebral artery occlusion (tMCAO) mouse model, the effects of MSC-EXs on the cerebral vascular ROS production and apoptosis, cerebral vascular density (cMVD), Evans blue extravasation, brain water content, neurological deficit score (NDS), and infarct volume were determined. Results MSC-EXs could deliver their carried miR-132-3p into target ECs, which functionally downregulated the target protein RASA1, while upregulated the expression of Ras and the downstream PI3K phosphorylation. Compared to MSC-EXs, MSC-EXsmiR-132-3p were more effective in decreasing ROS production, apoptosis, and tight junction disruption in H/R-injured ECs. These effects were associated with increased levels of phosphorylated Akt and eNOS, which could be abolished by PI3K inhibitor (LY294002) or Ras inhibitor (NSC 23766). In the tMCAO mouse model, the infusion of MSC-EXsmiR-132-3p was more effective than MSC-EXs in reducing cerebral vascular ROS production, BBB dysfunction, and brain injury. Conclusion Our results suggest that miR-132-3p promotes the beneficial effects of MSC-EXs on brain ischemic injury through protecting cerebral EC functions.

This study was to evaluate the efficacy of pharmaceutical intervention (PI) on chemotherapy knowledge-attitude-practice (KAP) and quality of life (QOL) in cancer patients. A prospective, randomized, controlled study was carried out at Oncology Ward in a tertiary hospital affiliated to Southern Medical University, China. Eligible patient was randomly assigned to pharmaceutical intervention (PI) group or control group. Each patient in PI group was given information booklets and was given 30 min face-to-face medication education and psychological counseling by clinical pharmacists, 2 sessions per week for 2 months. Patients in control group only received conventional treatment. All participants were asked to complete a structured Chemotherapy KAP Questionnaire and QOL Questionnaire at pre- and poststudy time. A total of 149 cancer patients (77 in PI group and 72 in control group) completed the study. The baseline scores of KAP and QOL in 2 groups were similar. At the end of study, only knowledge score was significantly increased; meanwhile no difference existed for attitude, practice, and QOL scores in control group; both KAP scores and QOL score were significantly increased in PI group. As for the between-group comparison, both KAP scores and QOL score in PI group were significantly higher than those in control group. In conclusion, pharmaceutical intervention has a positive role in increasing chemotherapy-related knowledge, improving patients' positive emotions, dealing with chemotherapy adverse reactions, and improving the quality of life of patients.

LMP1 expression is positively associated with metastasis in NPC, thus LMP1 detection in primary NPC might be an effective and feasible means to predict metastasis.

miR146a is well known for its regulatory role in the immune response and inflammation. Recent studies have demonstrated the links between miR146a and Alzheimer disease (AD) and suggested that miR146a may be involved in neuroinflammation and the metabolism of amyloid-β (Aβ), which are critical events in AD pathology. Although genetic studies have focused on the association between the miR146a gene and susceptibility to several diseases, no association study of miR146a variability with AD has been conducted. In this report, we performed a case-control association study to analyze the genotype and allele distributions of the miR146a, rs2910464 and rs57095329 polymorphisms in a Chinese population consisting of 292 AD cases and 300 healthy controls. We found a significant difference in the genotypes and allele frequencies of rs57095329 between the AD cases and the controls (p = 0.0147 and p = 0.0184, respectively), where the AA genotype of rs57095329 was associated with an increased risk of AD as well the cognitive decline in AD patients. Additionally, the AA genotype of rs57095329 exhibited significantly higher miR146a expression than the GG+GA genotypes of rs2910164 in the peripheral blood cells (PBMCs) of healthy individuals and had a stronger effect on the production of IL-6 and IL-1β when the cells were stimulated with LPS. Our data provide preliminary evidence that the rs57095329 polymorphism in the miR146a promoter is involved in the genetic susceptibility to AD, and this risk AA genotype may increase the expression of miR146a and influence certain proinflammatory cytokines, thus playing a role in the pathogenesis of AD.

No abstract

MicroRNA-125a-5p (miR-125a-5p) could participate in the pathogenesis of vascular diseases. In this study, we investigated the role of miR-125a-5p in oxidized low-density lipoprotein (ox-LDL)-induced functional changes in human brain microvessel endothelial cells (HBMEC). The reactive oxygen species (ROS) production, nitric oxide (NO) generation, senescence, apoptosis, and functions of HBMEC were analyzed. For mechanism study, the epidermal growth factor receptor (EGFR)/extracellular signal-regulated protein kinase (ERK)/p38 mitogen-activated protein kinase (p38 MAPK) pathway and phosphatidylinositol-3-kinase (PI3K)/serine/threonine kinase (Akt)/endothelial nitric oxide synthase (eNOS) pathway were analyzed. Results showed the following: ) Expression of miR-125a-5p was reduced in ox-LDL-treated HBMEC.) Overexpression of miR-125a-5p protected HBMEC from ox-LDL-induced apoptosis, senescence, ROS production, and NO reduction. ) Overexpression of miR-125a-5p increased HBMEC proliferation, migration, and tube formation, while decreasing HBMEC adhesion to leukocytes, as well as counteracting the effects of ox-LDL on those functions.) The levels of EGFR/ERK/p38 MAPK pathway, PI3K/Akt/eNOS pathway, cleaved caspase-3, and adherent molecular ICAM-1 and VCAM-1 were associated with the effects of ox-LDL on these HBMEC functions. In conclusion, miR-125a-5p could counteract the effects of ox-LDL on various HBMEC functions via regulating the EGFR/ERK/p38 MAPK and PI3K/Akt/eNOS pathways and cleaved caspase-3, ICAM-1, and VCAM-1 expression.

Unveiling the key mechanism of temporal lobe epilepsy (TLE) for the development of novel treatments is of increasing interest, and anti-inflammatory miR-146a is now considered a promising molecular target for TLE. In the current study, a C57BL/6 TLE mouse model was established using the lithium-pilocarpine protocol. The seizure degree was evaluated according to the Racine scale, and level 5 was considered the threshold for generalized convulsions. Animals were sacrificed to analyze the hippocampus at three time points (2 h and 4 and 8 weeks after pilocarpine administration to evaluate the acute, latent, and chronic phases, resp.). After intranasal delivery of miR-146a mimics (30 min before pilocarpine injection), the percent of animals with no induced seizures increased by 6.7%, the latency to generalized convulsions was extended, and seizure severity was reduced. Additionally, hippocampal damage was alleviated. While the relative miR-146a levels significantly increased, the expression of its target mRNAs (IRAK-1 and TRAF-6) and typical inflammatory modulators (NF-κB, TNF-α, IL-1β, and IL-6) decreased, supporting an anti-inflammatory role of miR-146a via the TLR pathway. This study is the first to demonstrate that intranasal delivery of miR-146a mimics can improve seizure onset and hippocampal damage in the acute phase of lithium-pilocarpine-induced seizures, which provides inflammation-based clues for the development of novel TLE treatments.

Mesenchymal stem cells (MSCs) show protective effects on ischemia/reperfusion- (I/R-) induced endothelial cell (EC) injury and vascular damage. Stem cell-released exosomes (EXs) could modulate target cell functions by delivering their cargos, and exert therapeutic effects as their mother cells. miR-126 is an important regulator of EC functions and angiogenesis. In this study, we determined whether EXs released from MSC-EXs provided beneficial effects on hypoxia/reoxygenation- (H/R-) injured ECs by transferring miR-126. MSCs were transfected with a miR-126 mimic or miR-126 short hairpin RNA to obtain miR-126-overexpressing MSC-EXs (MSC-EXsmiR-126) and miR-126 knockdown MSC-EXs (MSC-EXsSimiR-126). For functional studies, H/R-injured ECs were coincubated with various MSC-EXs. The viability, migration, tube formation ability, and apoptosis of ECs were measured. miR-126 and proangiogenic/growth factor (VEGF, EGF, PDGF, and bFGF) expressions were detected by qRT-PCR. Akt, p-Akt, p-eNOS, and cleaved caspase-3 expressions were examined by western blot. The PI3K inhibitor (LY294002) was used in pathway analysis. We found that overexpression/knockdown of miR-126 increased/decreased the proliferation of MSCs, as well as miR-126 expression in their derived MSC-EXs. MSC-EXsmiR-126 were more effective in promoting proliferation, migration, and tube formation ability of H/R-injured ECs than MSC-EXs. These effects were associated with the increase in p-Akt/Akt and p-eNOS, which could be abolished by LY294002. Besides, MSC-EXsmiR-126 were more effective than MSC-EXs in reducing the apoptosis of ECs, coupled with the decrease in cleaved caspase-3. Moreover, compared to MSC-EXs, MSC-EXsmiR-126 significantly upregulated the level of VEGF, EGF, PDGF, and bFGF in H/R-injured ECs. Downregulation of miR-126 in MSC-EXs inhibited these effects of MSC-EXs. The results suggest that MSC-EXs could enhance the survival and angiogenic function of H/R-injured ECs via delivering miR-126 to ECs and subsequently activate the PI3K/Akt/eNOS pathway, decrease cleaved caspase-3 expression, and increase angiogenic and growth factors.