Effect of gold-conjugated resveratrol nanoparticles on glioma cells and its underlying mechanism.

BACKGROUND:  Glioblastoma is the most aggressive brain tumor with poor prognosis. Although Resveratrol (Rsv) is known to have therapeutic effects on glioma, the effects of gold-conjugated resveratrol nanoparticles (Rsv-AuNPs) on glioma cells are rarely reported. OBJECTIVE: We aimed to investigate the effects of Rsv-AuNPs on glioma cells and its underlying mechanism. METHOD: Human glioma cell line U87 was treated with different concentrations of Rsv-AuNPs. CCK-8, transwell, and wound healing assay were performed to measure the effects of Rsv-AuNPs on cell proliferation, invasion, and migration ability, respectively. Flow cytometry assay was used to detect the effects of Rsv-AuNPs on apoptosis. Changes of protein expressions related to proliferation, invasion, migration, and apoptosis were measured by Western blot assay. In addition, the inhibitory role of Rsv-AuNPs in the PI3K/AKT/mTOR signaling pathway was verified by using PI3K inhibitor LY294002. RESULTS: Rsv-AuNPs treatment significantly suppressed proliferation, migration, and invasion of U87 cells (all P < 0.05) and increased the apoptosis rate (P < 0.05). The changes of proteins related to proliferation, migration, invasion and apoptosis were consistent (all P < 0.05). Moreover, Rsv-AuNPs treatment significantly inhibited the phosphorylation of PI3K, AKT and mTOR proteins in U87 cells (P < 0.05). CONCLUSION: The present study found that Rsv-AuNPs inhibited the proliferation, migration, and invasion of U87 cells and induced apoptosis by inhibiting the activation of PI3K/AKT/mTOR signaling pathway. In the future, Rsv-AuNPs might be applied to the clinical treatment of glioma through more in-depth animal and clinical research.

Mitochondrial transport in neurons and evidence for its involvement in acute neurological disorders.

Ensuring mitochondrial quality is essential for maintaining neuronal homeostasis, and mitochondrial transport plays a vital role in mitochondrial quality control. In this review, we first provide an overview of neuronal mitochondrial transport, followed by a detailed description of the various motors and adaptors associated with the anterograde and retrograde transport of mitochondria. Subsequently, we review the modest evidence involving mitochondrial transport mechanisms that has surfaced in acute neurological disorders, including traumatic brain injury, spinal cord injury, spontaneous intracerebral hemorrhage, and ischemic stroke. An in-depth study of this area will help deepen our understanding of the mechanisms underlying the development of various acute neurological disorders and ultimately improve therapeutic options.

Phosphatase and Tensin Homology Deleted on Chromosome 10 Inhibitors Promote Neural Stem Cell Proliferation and Differentiation.

Phosphatase and tensin homology deleted on chromosome 10 (PTEN) is a tumor suppressor gene. Its encoded protein has phosphatase and lipid phosphatase activities, which regulate the growth, differentiation, migration, and apoptosis of cells. The catalytic activity of PTEN is crucial for controlling cell growth under physiological and pathological conditions. It not only affects the survival and proliferation of tumor cells, but also inhibits a variety of cell regeneration processes. The use of PTEN inhibitors is being explored as a potentially beneficial therapeutic intervention for the repair of injuries to the central nervous system. PTEN influences the proliferation and differentiation of NSCs by regulating the expression and phosphorylation of downstream molecular protein kinase B (Akt) and the mammalian target of rapamycin (mTOR). However, the role of PTEN inhibitors in the Akt/mTOR signaling pathway in NSC proliferation and differentiation is unclear. Dipotassium bisperoxo (picolinoto) oxovanadate (V) [bpv(pic)] is a biologically active vanadium compound that blocks PTEN dephosphorylation and suppresses its activity, and has been used as a PTEN lipid phosphatase inhibitor. Here, bpv(pic) intervention was found to significantly increase the number of rat NSCs, as determined by bromodeoxyuridine staining and the cell counting kit-8, and to increase the percentage of neurons undergoing differentiation, as shown by immunofluorescence staining. Bpv(pic) intervention also significantly increased PTEN and mTOR expression, as shown by real-time PCR analysis and western blotting. In conclusion, PTEN inhibitor bpv(pic) promotes the proliferation and differentiation of NSCs into neurons.

Effect of Danhong injection on neurological recovery and adverse events in patients with acute ischemic stroke: A protocol for a randomized, double-blind, placebo-controlled clinical study.

BACKGROUND: Acute ischemic stroke (AIS) is characterized by high disabling and recurrent recurrence, and its severe neurological impairment and vascular adverse events (AEs) limit the recovery of patients. Danhong injection is a complementary alternative to the treatment of AIS, and previous studies have demonstrated its efficacy and safety. However, there is no long-term follow-up and rigorous clinical study to evaluate the effect of Danhong injection on neurological recovery and AEs in patients with AIS. METHODS: This is a prospective randomized, double-blind, placebo-controlled trial investigating the effect of Danhong injection on neurological recovery and AEs in patients with AIS. Participants were randomly divided into treatment and control groups in a 1:1 ratio. The treatment group was treated with Danhong injection and the control group were treated with placebo under the guideline recommended basic treatment. After 14 days of continuous treatment, the follow-up period was 6 months. Observation indicators include: National Institute of Health Stroke Scale, modified Rankin scale, symptomatic intracranial hemorrhage, the incidence of new major vascular events within 6 months, and all-cause mortality. Finally, the data were analyzed statistically using the SPASS 22.0 software. DISCUSSION: This study will evaluate the effect of Danhong injection on neurological recovery and AEs in AIS. The results will provide a reference for the clinical use of AIS.

Targeting PTEN to regulate autophagy and promote the repair of injured neurons.

The effects of autophagy on neuronal damage can be positive or detrimental negative. Through establishing a model of fetal rat cortical neuron hydraulic shock injury, dipotassium bisperoxo (picolinoto) oxovanadate (V) [bpv(pic)] was used to inhibit PTEN at different time points post-injury and autophagy level after neuronal injury was assessed. Neurons were divided into several intervention groups according to the time point at which bpv(pic) was used to inhibit autophagy, normal neurons and injuried neurons were set as two control groups. Growth of neurons in each group was assessed through immunofluorescence staining. Expression of the autophagy-related proteins LC3-II and LC3-I was analyzed by western blot. Expression of PTEN, mTOR and Beclin-1 was detected by RT-PCR. The number of autophagosomes in the normal group, injury control group and 24 h, 36 h intervention groups were assessed by electron microscope. We found that autophagy was enhanced after neuronal injury and that the levels of LC3-II was significantly reduced by bpv (pic) intervention. The growth of the injury control groups was worse than normal groups, while improved through bpv(pic) intervention at 24 h and 30 h after injured. Western blot analysis showed that the LC3-II and LC3-II/LC3-I ratios of cells increased post-injury, and autophagy induction was evident by electron microscopy. These effects were confirmed by RT-PCR analysis. Taken together, these data suggest that autophagy is activated after injury in neurons while can be inhibited by bpv(pic) administration and then promote the repair of injured neurons.

Hippocampal PPARα is involved in the antidepressant-like effects of venlafaxine in mice.

Although thought as a serotonin and norepinephrine reuptake inhibitor (SNRI), the antidepressant mechanisms of venlafaxine remain unknown. Previous reports have shown the role of peroxisome proliferator activated receptor α (PPARα) in depression. In this study, we investigated whether the antidepressant-like effects of venlafaxine require PPARα. We first examined whether repeated venlafaxine administration reversed the effects of chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS) on PPARα in the hippocampus and medial prefrontal cortex (mPFC). Then, the pharmacologcial inhibitors of PPARα, GW6471 and MK886, were used to assay if the protecting effects of venlafaxine against chronic stress were prevented by PPARα blockade. Furthermore, gene knockdown of PPARα by AAV-PPARα-shRNA was also used. It was found that venlafaxine treatment fully restored the decreasing effects of CUMS and CRS on the hippocampal PPARα expression. Pharmacological inhibition of PPARα significantly attenuated the antidepressant-like effects of venlafaxine in mice. Moreover, gene knockdown of hippocampal PPARα also fully abolished the antidepressant-like actions of venlafaxine in mice. Collectively, hippocampal PPARα is an antidepressant target of venlafaxine.

Impacts of phosphatase and tensin homology deleted on chromosome ten (PTEN)-inhibiting chitosan scaffold on growth and differentiation of neural stem cells.

OBJECTIVE: The aim of this study was to investigate growth and differentiation of neural stem cells (NSCs) on the phosphatase and tensin homology deleted on chromosome ten (PTEN)-inhibitor-adsorbed chitosan scaffold. METHODS: NSCs were divide into the chitosan group and the control groups, and performed CCK-8 test on 1(st), 3(rd) and 7(th) d to compare the proliferation between the 2 groups. The chitosan scaffold adsorbed PTEN inhibitor bpv (pic), and the empty scaffold was used as the control for co-culture of NSCs, immunofluorescence staining was performed on 7(th) d to detect the differentiation of NSCs on the scaffold. RESULTS: The results of CCK-8 test showed no significant difference in the absorbance between the 2 groups. Immunofluorescence staining showed that the NSCs numbers of the bpv scaffold group were more than the empty scaffold group, among which the anti-glial fibrillary acidic protein (GFAP) positive cells were less than the empty scaffold group, while the anti-ß-Tubulin III positive cells were more than the empty scaffold group, the two groups both showed rare anti-receptor-interacting protein (RIP) positive cells. CONCLUSIONS: Chitosan scaffold exhibited good compatibility to NSCs, the PTEN-inhibitor-adsorbed chitosan scaffold could promote the migration of NSCs towards the scaffold and their differentiation towards neurons.

No Evidence of Increased Risk of Stroke with Consumption of Refined Grains: A Meta-analysis of Prospective Cohort Studies.

OBJECTIVES: Results of the relationships between dietary consumption of refined grains and the risk of stroke are mixed. This study was based on a meta-analysis of prospective cohort studies. METHODS: We systematically searched the MEDLINE (from January 1, 1966) and EMBASE (from January 1, 1974) databases up to November 30, 2014. Random-effects models were used to calculate summary relative risks (SRRs) and 95% confidence intervals (CIs). Between-study heterogeneity was assessed using Cochran's Q and I(2) statistics. RESULTS: Eight prospective studies (7 publications) with a total of 410,821 subjects and 8284 stroke events were included in the meta-analysis. Overall, a diet containing greater amounts of refined grains was not associated with risk of stroke, with no evidence of heterogeneity among studies (SRR = 1.02; 95% CI, .93-1.10; P(heterogeneity) = .970; I(2) = 0). In addition, no significant associations between consumption of refined grains and risk of stroke were found for both women and men, for both hemorrhagic and ischemic strokes, and for both incident and fatal strokes. These null results are consistent with those of linear dose-response meta-analyses (SRR = .98; 95% CI, .73-1.03 for per 3 servings/day). Consumption of white rice was not associated with risk of stroke (SRR = 1.01; 95% CI, .93-1.11; P(heterogeneity) = .966; I(2) = 0). CONCLUSIONS: The current meta-analysis provides some evidence for the hypothesis that consumption of refined grains was not associated with risk of stroke and its subtypes.

Application of microarray technology for the detection of intracranial bacterial infection.

The aim of this study was to assess the value of microarray technology for the detection of intracranial bacterial infection. A small gene chip was prepared based on the four pathogens commonly known to cause intracranial infection and the corresponding six types of common resistance genes in The Affiliated Hospital of Nantong University and The Affiliated Haian People's Hospital of Nantong University. Cerebrospinal fluid samples were then collected from 30 patients with clinically diagnosed intracranial infection for the detection of the bacteria and resistance genes. The results were compared with the bacterial culture and sensitivity test results from the Department of Clinical Laboratories. The laboratory bacterial culture took 4-5 days, and revealed that 12 cases were positive and 18 cases were negative for bacteria. The microarray analysis took 1 day, and bacteria and resistance genes were detected in 15 cases. The 16S gene and drug resistance genes were detected in 8 cases; however, the bacterial strain was not identified. Seven cases appeared negative for bacteria and resistance genes. Microarray technology is rapid, sensitive and suitable for use in the detection of intracranial infections and other diseases for which conventional bacterial culture has a low positive rate.