Stormspivey8186

Epilepsy is a common neurological disease that can induce severe physiological brain damage, including nerve cell apoptosis. MicroRNAs (miRs) have been widely investigated in epilepsy therapy. miR-135a-5p expression levels in children with temporal lobe epilepsy were found to be significantly increased. However, whether miR-135a-5p participates in epilepsy-induced cell apoptosis is not completely understood. In the present study, an in vitro model of epilepsy in BV2 microglia cells was induced using 6-µm kainic acid (KA). Reverse-transcription quantitative PCR was performed to analyze miR-135a-5p and sirtuin 1 (SIRT1) mRNA expression levels. Western blotting was performed to measure SIRT1 protein expression levels. BV2 cell proliferation and apoptosis were assessed by performing MTT assays and flow cytometry, respectively. A BCA protein assay kit was used to detect caspase-3 and caspase-9 activities. TargetScan and dual luciferase reporter assays were performed to investigate the interaction between miR-135a-5p and the 3'-untranslated region (UTR) of SIRT1. miR-135a-5p expression was significantly increased in the KA-induced in vitro model of epilepsy in BV2 microglia. miR-135a-5p inhibitor effectively promoted BV2 microglia proliferation and inhibited microglia apoptosis, whereas small interfering RNA targeting SIRT1 significantly repressed BV2 microglia proliferation and induced microglia apoptosis. In addition, the results demonstrated that the 3'-UTR of SIRT1 mRNA was targeted by miR-135a-5p, and SIRT1 knockdown attenuated miR-135a-5p inhibitor-mediated effects on epilepsy. In summary, the results of the present study identified the role of miR-135a-5p inhibitor pretreatment in protecting nerve cells against epilepsy-induced apoptosis and provided a novel strategy for the treatment of neural damage in seizures.Orthodontic tooth movement (OTM) has been widely observed worldwide. The OTM process is involved in several biological activities and can result in temporary hypoxia. The dynamic changes of autophagy and apoptosis during OTM have not, to the best of our knowledge, been previously reported. In the present study, an OTM animal model was established. Periodontal ligament cells (PDLCs) and osteoclasts were investigated using H&E and tartrate-resistant acid phosphatase staining. The changes in the expression levels of certain autophagy and apoptotic markers were investigated using immunohistochemical staining. A significant decrease in PDLC and an increase in osteoclast numbers were observed 1 day following OTM induction. The expression levels of Beclin-1 and LC3-II peaked at 1 h post-OTM, followed by a gradual decrease. Milciclib The expression levels of P62 in each experimental group were significantly lower than those noted in the 0 h group. The expression levels of Bcl-2 were markedly increased 1 h following OTM and reached a maximum at 1 day post-OTM. The highest expression levels of Bax and caspase-3 were observed 7 days following OTM induction. The present study provided additional information regarding the involvement of autophagy and apoptotic markers in the OTM process and aided the understanding of the initiation and pathophysiological progression of this condition.The aim of the present study was to demonstrate that Fritillaria thunbergii Miquel extract exerts anti-inflammatory and antioxidant effects on lipopolysaccharide-stimulated RAW 264.7 cells. To confirm the inhibitory effect of ethyl acetate fraction of FTM (EAFM) on inflammation, the expression of nitric oxide (NO) and inflammatory cytokines was assessed by performing ELISA. Expression of intracellular mRNA and protein was confirmed by reverse transcription PCR and western blotting. In addition, the anti-inflammatory and anti-oxidant mechanisms of NF-κB, MAPK and heme oxygenase-1 (HO-1) were also investigated. EAFM significantly inhibited the expression of inflammatory factors including NO, IL-6 and TNF-α at non-toxic concentrations. EAFM also inhibited the mRNA and protein expression of inducible nitric oxide synthase in a concentration-dependent manner, but did not alter the expression of cyclooxygenase-2. Pre-treatment with EAFM inhibited the nuclear translocation of NF-κB, and suppressed the phosphorylation of ERK and JNK. In addition, EAFM induced 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity and an increase in the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1. The results indicated that EAFM inhibited the expression of pro-inflammatory cytokines by inhibiting ERK/JNK phosphorylation and NF-κB translocation. EAFM also exerted antioxidant effects via Nrf2/HO-1 stimulation. Collectively, the results of the present study indicated that EAFM may be a valuable alternative for the treatment of a variety of inflammatory diseases.Huanglian-Houpo drug combination (HHDC) is a classical traditional Chinese medicine that has been effectively used to treat seasonal colds and flu. However, no systematic studies of the effects of HHDC on H1N1 influenza infection and the associated mechanisms have been reported. The aim of the present study was to determine the anti-H1N1 influenza effects of HHDC and explore the underlying mechanisms. A mouse model of H1N1-induced pneumonia was established and the mice were treated with HHDC (4, 8 and 16 g/kg) for 5 days after viral challenge. The antiviral effects of HHDC and the underlying mechanisms in the mice were investigated and evaluated with respect to inflammation, oxidative stress and Toll-like receptor (TLR)/myeloid differentiation factor (MyD88)/nuclear factor (NF)-κB signaling pathways. HHDC provided significant protection against weight loss and reduced the H1N1 viral load in the lungs. In addition, HHDC significantly decreased the lung index and increased the spleen and thymus indices of the H1N1-infected mice. HHDC also significantly ameliorated the histopathological changes of pneumonia, decreased serum levels of the cytokines interleukin (IL)-6, tumor necrosis factor-α and interferon-γ, and increased the serum level of IL-2. Moreover, HHDC significantly increased the levels of the antioxidant factors superoxide dismutase and glutathione, and reduced the serum level of nitric oxide. Furthermore, the mRNA and protein expression levels of TLR3, TLR7, MyD88, NF-κB p65 and tumor necrosis factor receptor-associated factor 3 in the lung tissues were significantly decreased by HHDC. These findings suggest that HHDC directly inhibited H1N1 infection in vivo and exerted a therapeutic effect on influenza-induced pneumonia in mice by modulating cytokines, antioxidant factors and TLR/MyD88/NF-κB signaling pathways.The aim of the present study was to compare the effects of two methods of dexmedetomidine (Dex) administration on myocardial injury, inflammation and stress in ischemic myocardium during rheumatic heart valve replacement. In total, 90 patients were included in the present study and were divided into the following three groups i) Dex group (1.0 µg/kg Dex pre-administered 10 min prior to anesthesia, then 0.5 µg/kg/h Dex for maintenance); ii) Dex pre-conditioning group (Pre-Dex; 1.0 µg/kg Dex administered 10 min prior to anesthesia, then saline for maintenance); and iii) control group (saline 10 min prior to anesthesia and saline during maintenance), with 30 patients in each group. Heart rate (HR) and mean artery pressure (MAP) were recorded at eight time-points i) T1, pre-medication; ii) T2, 10 min post-medication; iii) T3, immediately post-intubation; iv) T4, upon skin incision; v) T5, upon sawing the sternum; vi) T6, immediately post-cardiopulmonary bypass; vii) T7, immediately post-operation; and viii) T8, 24 h post-operation. The serum cardiac troponin I (cTnI), interleukin (IL)-8, IL-10 and malondialdehyde (MDA) levels were also detected at T1, T6, T7 and T8. Blood glucose levels were detected at T1, T5, T6 and T7. In comparison with the control group, patients in the Dex group exhibited a significant increase in cardiac function, as indicated by an increase in HR, MAP and IL-10 levels, and a significant decrease in cTnI, IL-8, MDA and glucose levels. Both Dex perfusion and Dex preconditioning were able to reduce myocardial injury, inflammation, oxidative stress and stress response in rheumatic heart valve replacement surgery. However, Dex perfusion during the whole surgery was more effective than Dex preconditioning treatment. The study was registered with the Chinese Clinical Trial Registry (ChiCTR; no. ChiCTR-INR-17011955).Autophagy serves an important role in amyloid-β (Aβ) metabolism and τ processing and clearance in Alzheimer's disease. The progression of Aβ plaque accumulation and hyperphosphorylation of τ proteins are enhanced by oxidative stress. A hydrogen peroxide (H2O2) injury cell model was established using SH-SY5Y cells. Cells were randomly divided into normal, H2O2 and chlorogenic acid (5-caffeoylquinic acid; CGA) groups. The influence of CGA on cell viability was evaluated using a Cell Counting Kit-8 assay and cell death was assessed using Hoechst 33342 nuclear staining. Autophagy induction and fusion of autophagic vacuoles assays were performed using monodansylcadaverine staining. Additionally, SH-SY5Y cells expressing Ad-mCherry-green fluorescent protein-LC3B were established to detect autophagic flow. LysoTracker Red staining was used to evaluate lysosome function and LysoSensor™ Green staining assays were used to assess lysosomal acidification. The results demonstrated that CGA decreased the apoptosis rate, increased cell viability and improved cell morphology in H2O2-treated SH-SY5Y cells. Furthermore, CGA alleviated the accumulation of autophagic vacuoles, reduced the LC3BII/I ratio and decreased P62 levels, resulting in increased autophagic flux. Additionally, CGA upregulated lysosome acidity and increased the expression levels of cathepsin D. Importantly, these effects of CGA on H2O2-treated SH-SY5Y cells were mediated via the mTOR-transcription factor EB signaling pathway. These results indicated that CGA protected cells against H2O2-induced oxidative damage via the upregulation of autophagosomes, which promoted autophagocytic degradation and increased autophagic flux.The incidence of diabetic encephalopathy is increasing as the population ages. Evidence suggests that formation and accumulation of advanced glycation end products (AGEs) plays a pivotal role in disease progression, but limited research has been carried out in this area. A previous study demonstrated that Kuwanon G (KWG) had significant anti-oxidative stress and anti-inflammatory properties. As AGEs are oxidative products and inflammation is involved in their generation it is hypothesized that KWG may have effects against AGE-induced neuronal damage. In the present study, mouse hippocampal neuronal cell line HT22 was used. KWG was shown to significantly inhibit AGE-induced cell apoptosis in comparison with a control treatment, as determined by both MTT and flow cytometry. Compared with the AGEs group, expression of pro-apoptotic protein Bax was reduced and expression of anti-apoptotic protein Bcl-2 was increased in the AGEs + KWG group. Both intracellular and extracellular levels of acetylcholine and choline acetyltransferase were significantly elevated after KWG administration in comparison with controls whilethe level of acetylcholinesterase decreased.