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Objective: To study the effect of miR-16-5p on lung cancer cell injury and apoptosis, and its mechanism. Methods: LPS induced lung cancer cell A549 injury; qRT-PCR method was applied to detect the expression of miR-16-5p and CXCR3 in A549 cells. Con (without LPS treatment), LPS + miR-NC group (transfected negative control samples), LPS + miR-16-5p group (transfected miR-16-5p mimics); LPS + si-NC group (transfected negative control samples), LPS + si-CXCR3 group (transfected si-CXCR3); LPS + miR-16-5p + pcDNA3.1 group (co-transfected miR-16-5p mimics and pcDNA3.1), LPS + miR-16-5p + pcDNA3.1-CXCR3 group (co-transfected miR-16-5p mimics and pcDNA3.1-CXCR3) were transfected into A549 cells by liposome method. Western blot was used to detect protein expression of CXCR3, IL-6 and TNF-α in A549 cells; apoptosis of A549 cells was detected by flow cytometry. Results: Compared with the control group, the expression of miR-16-5p mRNA was significantly decreased in A549 cells in LPS group, and the mRNA and protein expression of CXCR3 were significantly increased (p <.05). Overexpression of miR-16-5p and knockdown of CXCR3 both can down-regulated protein expression of IL-6 and TNF-α, and up-regulated apoptosis in LPS-induced A549 cell; CXCR3 is a target of miR-16-5p. Overexpression of CXCR3 rescued the protective effect of miR-16-5p on LPS-induced A549 cell injury. Conclusion: miR-16-5p can protect LPS-induced A549 cell injury, and its mechanism may be related to the targeted regulation of CXCR3, which could provide a new target for targeted therapy of lung cancer. [ABSTRACT FROM AUTHOR]

Abstract: We synthesized a series of novel small molecules, 2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine derivatives, by tandem reduction-oxirane opening of 2-nitroaroxymethyloxiranes in moderate or excellent yields. We investigated the effects of all of the compounds on HUVEC apoptosis and A549 cell growth. The results showed that 6,8-dichloro-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine was the most effective small molecule in promoting HUVEC apoptosis and inhibiting A549 cell proliferation, but 6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine could remarkably inhibit HUVEC apoptosis and might induce the formation of microvessel. [Copyright &y& Elsevier]

Background: Omega 3 polyunsaturated fatty acid (Omega-3PUFA) is one of the essential nutrients for human body involved in intracellular metabolic regulation and cell signaling. Previous studies have shown that Omega-3PUFA is involved in the pathogenesis of digestive system tumors, including colorectal cancer (CRC), however, the effects of Omega-3PUFA on CRC has not been fully elucidated. In the current study, we evaluated whether Omega-3PUFA can alleviate N-methyl-N-nitrosourea(MNU) induced CRC in a rat model and illustrated the potential mechanism. Methods: The effects of Omga-3PUFA on MNU-induced colorectal cancer in rats were analyzed by in vivo experiments. The viability, apoptosis, colony formation and invasion of CRC cells treated with Omga-3PUFA were detected by CCK8, flow cytometry, clone formation assay and transwell invasion assay. The expression of apoptosis-related proteins in CRC cells treated with Omga-3PUFA was detected by Western blotting. Finally, after adding PI3K activator, the viability, apoptosis and protein expression of CRC cells treated with Omga-3PUFA were detected by CCK8, flow cytometry and Western blotting. Results: Our results showed that Omega-3PUFA attenuated MNU-induced CRC in rats and inhibited AKT/Bcl-2 signaling in rats. In addition, Omega-3PUFA inhibited CRC cell proliferation and induces CRC cell apoptosis. Moreover, Omega-3PUFA inhibited CRC cell colony formation and invasion, and inhibited PI3K/AKT/Bcl-2 signaling in CRC cells. Furthermore, The effects of Omega-3PUFA on cell proliferation and apoptosis were inhibited by blocking PI3K/AKT signaling. Conclusion: Omega-3PUFA can attenuate MNU-induced colorectal cancer in rats by blocking PI3K/AKT/Bcl-2 signaling, which suggests that Omega-3PUFA may be a potent agent for CRC treatment. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRs) were involved in numerous cardiovascular diseases, especially ischemic heart diseases, but the miR changes during cardiac ischemia–reperfusion (I/R) injury following sevoflurane (SEV) preconditioning are still unknown. This study aims to investigate the effect of miR‐874 on cardiac I/R injury in mouse models pretreated with SEV. Following establishment of mouse models with myocardial I/R injury, mice were pretreated with SEV. The functional mechanism of miR‐874 in I/R injury was explored when miR‐874 and the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway were inhibited. Terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP biotin nick‐end labeling (TUNEL) staining was used to detect cardiomyocyte apoptosis and dual luciferase reporter gene assay to identify the targeting relationship between miR‐874 and STAT3. Expression of the JAK2/STAT3 signaling pathway and apoptosis‐related genes was determined. Initially, upregulated miR‐874 was observed in I/R mice. Then, miR‐874 inhibition improved cardiac function of I/R mice, inhibited cardiomyocyte apoptosis (also shown as decreased Bcl‐2 associated X protein B [Bax] and increased B‐cell lymphoma‐2 [Bcl‐2]), and activated the JAK2/STAT3 signaling pathway. STAT3, a target gene of miR‐874, was upregulated following miR‐874 inhibition. Finally, we also observed that the effect of miR‐874 was lost when the JAK2/STAT3 signaling pathway was blocked. The findings indicate miR‐874 as a contributory role in cardiac I/R injury, with miR‐874 inhibition alleviating cardiac I/R injury in mice following SEV pretreatment by targeting STAT3 through the JAK2/STAT3 signaling pathway. The findings indicate microRNA (miR)‐874 as a contributory role in cardiac ischemia–reperfusion injury (I/R) injury, with miR‐874 inhibition alleviating cardiac I/R injury in mice following sevoflurane pretreatment by targeting signal transducer and activator of transcription 3 (STAT3) through the Janus kinase 2 (JAK2)/STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]

Living donor liver transplantation (LDLT) requires ischemia/reperfusion (I/R), which can lead to early graft injury. However, the detailed molecular mechanism of I/R injury remains unclear. Carnosic acid, as a phenolic diterpene with function of anti-inflammation, anti-cancer, anti-bacterial, anti-diabetic, as well as neuroprotective properties, is produced by many species from Lamiaceae family. Nanoparticulate drug delivery systems have been known to better the bioavailability of drugs on intranasal administration compared with only drug solutions. Administration of carnosic acid nanoparticles was thought to be sufficient to lead to considerable inhibition of liver injury progression induced by ischemia/reperfusion. In our study, liver ischemia/reperfusion injury was established successfully with C57BL/6 animal model. 10 and 20 mg/kg carnosic acid nanoparticles were injected to mice for five days prior to ischemia. After liver ischemia/reperfusion, the levels of serum AST, ALT and APL were increased, which was attenuated by pre-treatment with carnosic acid nanoparticles. In addition, carnosic acid nanoparticles inhibited ROS production via its related signals regulation. And carnosic acid nanoparticles also suppressed the ischemia/reperfusion-induced up-regulation in the pro-apoptotic protein and mRNA levels of Bax, Cyto-c, Apaf-1 and Caspase-9/3 while increased ischemia/reperfusion-induced decrease of anti-apoptotic factor of Bcl-2. Further, ischemia/reperfusion-induced inflammation was also inhibited for carnosic acid nanoparticles administration via inactivating NF-κB signaling pathway, leading to down-regulation of pro-inflammatory cytokines releasing. In conclusion, our study suggested that carnosic acid nanoparticles protected against liver ischemia/reperfusion injury via its role of anti-oxidative, anti-apoptotic and anti-inflammatory bioactivity. [ABSTRACT FROM AUTHOR]

Despite considerable efficacy of arsenic trioxide (As2O3) in acute promyelocytic leukemia (APL) treatment, other non-APL leukemias, such as chronic myeloid leukemia (CML), are less sensitive to As2O3 treatment. However, the underlying mechanism is not well understood. Here we show that relative As2O3-resistant K562 cells have significantly lower ROS levels than As2O3-sensitive NB4 cells. We compared the expression of several antioxidant enzymes in these two cell lines and found that peroxiredoxin 1/2/6 and catalase are expressed at high levels in K562 cells. We further investigated the possible role of peroxirdoxin 1/2/6 and catalase in determining the cellular sensitivity to As2O3. Interestingly, knockdown of peroxiredoxin 1/2/6 did not increase the susceptibility of K562 cells to As2O3. On the contrary, knockdown of catalase markedly enhanced As2O3-induced apoptosis. In addition, we provide evidence that overexpression of BCR/ABL cannot increase the expression of PRDX 1/2/6 and catalase. The current study reveals that the functional role of antioxidant enzymes is cellular context and treatment agents dependent; targeting catalase may represent a novel strategy to improve the efficacy of As2O3 in CML treatment. [ABSTRACT FROM AUTHOR]

Hydrogen sulphide ( H2S), one of three signalling gasotransmitters, plays an important role in oxidative stress and apoptosis. However, the effects of H2S on oxidative stress-induced apoptosis in focal cerebral ischaemic injury in rats have not been clarified., In the present study, sodium hydrosulphide ( NaHS) was used as the H2S donor. Eighty-four Sprague- Dawley rats were randomly divided into six groups: sham, sham + low-dose (2.8 mg/kg) NaHS, sham + high-dose (11.2 mg/kg) NaHS, infarct, infarct + low-dose NaHS and infarct + high-dose NaHS. The focal cerebral ischaemic model was created by cranially inserting a nylon thread with a rounded tip into an internal carotid artery. Rats were killed 21 h after administration of NaHS., In the infarct + low-dose NaHS compared with infarct group, infarct volume was significantly decreased and injury to the mitochondria in nerve cells was mitigated. Furthermore, significant increases were seen in mitochondrial superoxide dismutase and glutathione peroxidase activity and neuronal bcl-2 protein levels, whereas mitochondrial malondialdehyde content and neuronal bax and caspase 3 protein levels were significantly decreased, in the infarct + low-dose NaHS compared with infarct group. The effects seen in the infarct group were significantly aggravated in the infarct + high-dose NaHS group., The findings of the present study provide novel evidence for the dual effects of H2S on focal cerebral ischaemic injury via modulation of oxidative stress-induced apoptosis. [ABSTRACT FROM AUTHOR]