Elevated circulating miR-494 in plasma of children with enterovirus 71 induced hand, foot, and mouth disease and its potential diagnostic value.

Hand, foot, and mouth disease (HFMD) is a common pediatric disease, whose outcome depends of the enterovirus genotype infecting the patient. The present study is focused on the potential diagnostic value and the role of circulating microRNA-494 (miR-494) in enterovirus 71-induced more severe form of HFMD. We included 102 children with enterovirus 71 (EV71)-induced HFMD, 42 coxsackievirus A16 (CA16)-induced HFMD and 102 healthy controls. The plasma and serum samples were collected. The expression level of circulating miR-494 was determined by RT-PCR method. Moreover, ROC curve has been drawn to evaluate the sensitivity and specificity of circulating miR-494 for the diagnosis of EV71-induced HFMD. Furthermore, the correlation between the circulating miR-494 and the levels of interleukin 6 (IL-6), interleukin 4 (IL-4) and interferon γ (IFN-γ) in the serum of patients were analyzed. Circulating miR-494 was significantly increased in plasma of children with EV71-induced HFMD compared with the healthy children or CA16-induced HFMD, and level of miR-494 in the EV71 severe group was significantly higher than the EV71 mild group. Moreover, results of ROC analysis suggested that miR-494 is a sensitive biomarker to distinguish EV71 patients from healthy controls and CA16 patients. Furthermore, IL-6 and IFN-γ were elevated in serum of patients with EV71-induced HFMD and the level of circulating miR-494 in patients with EV71-induced HFMD was positively correlated with the serum levels of both IL-6 and IFN-γ, respectively. Circulating miR-494 was abnormally up-regulated in plasma of the children with EV71-induced HFMD, and miR-494 may serve as potential biomarker for the diagnosis and treatment of the disease. Keywords: miR-494; HFMD; biomarker; enterovirus 71; inflammation.

[Exploration of omics mechanism and drug prediction of coronavirus-induced heart failure based on clinical bioinformatics].

Objective: Present study investigated the mechanism of heart failure associated with coronavirus infection and predicted potential effective therapeutic drugs against heart failure associated with coronavirus infection. Methods: Coronavirus and heart failure were searched in the Gene Expression Omnibus (GEO) and omics data were selected to meet experimental requirements. Differentially expressed genes were analyzed using the Limma package in R language to screen for differentially expressed genes. The two sets of differential genes were introduced into the R language cluster Profiler package for gene ontology (GO) and Kyoto gene and genome encyclopedia (KEGG) pathway enrichment analysis. Two sets of intersections were taken. A protein interaction network was constructed for all differentially expressed genes using STRING database and core genes were screened. Finally, the apparently accurate treatment prediction platform (EpiMed) independently developed by the team was used to predict the therapeutic drug. Results: The GSE59185 coronavirus data set was searched and screened in the GEO database, and divided into wt group, ΔE group, Δ3 group, Δ5 group according to different subtypes, and compared with control group. After the difference analysis, 191 up-regulated genes and 18 down-regulated genes were defined. The GEO126062 heart failure data set was retrieved and screened from the GEO database. A total of 495 differentially expressed genes were screened, of which 165 were up-regulated and 330 were down-regulated. Correlation analysis of differentially expressed genes between coronavirus and heart failure was performed. After cross processing, there were 20 GO entries, which were mainly enriched in virus response, virus defense response, type Ⅰ interferon response, γ interferon regulation, innate immune response regulation, negative regulation of virus life cycle, replication regulation of viral genome, etc. There were 5 KEGG pathways, mainly interacting with tumor necrosis factor (TNF) signaling pathway, interleukin (IL)-17 signaling pathway, cytokine and receptor interaction, Toll-like receptor signaling pathway, human giant cells viral infection related. All differentially expressed genes were introduced into the STRING online analysis website for protein interaction network analysis, and core genes such as signal transducer and activator of transcription 3, IL-10, IL17, TNF, interferon regulatory factor 9, 2'-5'-oligoadenylate synthetase 1, mitogen-activated protein kinase 3, radical s-adenosyl methionine domain containing 2, c-x-c motif chemokine ligand 10, caspase 3 and other genes were screened. The drugs predicted by EpiMed's apparent precision treatment prediction platform for disease-drug association analysis were mainly TNF-α inhibitors, resveratrol, ritonavir, paeony, retinoic acid, forsythia, and houttuynia cordata. Conclusions: The abnormal activation of multiple inflammatory pathways may be the cause of heart failure in patients after coronavirus infection. Resveratrol, ritonavir, retinoic acid, amaranth, forsythia, houttuynia may have therapeutic effects. Future basic and clinical research is warranted to validate present results and hypothesis.

[Observation of the clinical efficacy of tigecycline for treatment of ventilator-associated pneumonia in critically ill elderly patients].

OBJECTIVE: To evaluate the efficacy of tigecycline for treatment of ventilator-associated pneumonia in critically ill elderly patients. METHODS: Data of critically ill elderly patients with ventilator-associated pneumonia treated with tigecycline in the intensive care unit was collected from June 2011 to March 2014 in this retrospective study, to evaluated the clinical efficacy of tigecycline. RESULTS: A total of 79 patients (83.5% male) were included, the mean age was 84 years old (rang, 65 years to 100 years old). Acinetobacter baumannii (39.1%), Pseudomonas aeruginosa (35.0%) and Klebsiella pneumonia (23.8%) were the most common pathogens.All patients were treated with tigecycline, 54.4% combined with other antimicrobial agents, 35.4% treated with double dose of tigecycline, and the mean course of antibiotic treatment was 9 days (range, 2 days to 22 days). After treatment, clinical success were recorded in 44 patients (55.7%), clinical failure were recorded in 29 patients, clinical uncertainty were recorded in 6 patients.28 days after treatment, patients' overall mortality was 39.0%.The clinical success rates were associated with acute physiology and chronic health evaluation (APACHE) Ⅱ score less than 15 (the clinical success rates were 72.2% and 41.9% in patients with APACHE Ⅱ score<15 and APACHE Ⅱ score≥15, respectively; P=0.007); treated with double dose of tigecycline (71.4% vs 47.1%, P=0.037) or combination regimens were also had significant difference (67.4% vs 41.7%, P=0.022). CONCLUSIONS: Treatment of tigecycline combined with other antimicrobial agents and double dose of tigecycline may both can improve clinical efficacy in critically ill elderly patients with ventilator-associated pneumonia.

Design, modeling, and testing of a one degree of freedom manipulator with three-stage amplification mechanism.

The one degree of freedom (1-DOF) manipulator with nano-resolution is a significant component in the micro-/nano-manipulation. In order to simultaneously achieve a large stroke and high precision, a piezo-driven 1-DOF flexure-based manipulator consisting of an enhanced double Scott-Russell mechanism (EDSRM), a lever type mechanism, and a Z-shaped mechanism is proposed in this paper. Analytical models are developed to examine the kinetostatic and dynamic properties of the manipulator. A finite element analysis is further performed to evaluate the characteristics of the EDSRM and the complete manipulator. The prototype is fabricated on monolithic AL7075, and various experimental tests have been carried out to investigate the correctness of the modeling. The experimental results show that the proposed manipulator has a satisfactory amplification ratio, static stability, and dynamic performance.

Selective inhibition of NAALADase, which converts NAAG to glutamate, reduces ischemic brain injury.

We describe here a new strategy for the treatment of stroke, through the inhibition of NAALADase (N-acetylated-alpha-linked-acidic dipeptidase), an enzyme responsible for the hydrolysis of the neuropeptide NAAG (N-acetyl-aspartyl-glutamate) to N-acetyl-aspartate and glutamate. We demonstrate that the newly described NAALADase inhibitor 2-PMPA (2-(phosphonomethyl)pentanedioic acid) robustly protects against ischemic injury in a neuronal culture model of stroke and in rats after transient middle cerebral artery occlusion. Consistent with inhibition of NAALADase, we show that 2-PMPA increases NAAG and attenuates the ischemia-induced rise in glutamate. Both effects could contribute to neuroprotection. These data indicate that NAALADase inhibition may have use in neurological disorders in which excessive excitatory amino acid transmission is pathogenic.

LncRNA LINP1 promotes proliferation and inhibits apoptosis of gastric cancer cells by repressing RBM5.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "LncRNA LINP1 promotes proliferation and inhibits apoptosis of gastric cancer cells by repressing RBM5, by X.-C. Lu, H.-Y. Zhou, J. Wu, Y. Jin, X.-M. Yao, X.-Y. Wu, published in Eur Rev Med Pharmacol Sci 2020; 24 (1): 137-144-DOI: 10.26355/eurrev_202001_19904-PMID: 31957826" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19904.

Long non-coding RNA AB073614 promotes metastasis of gastric cancer cells by upregulating IGF-2.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long non-coding RNA AB073614 promotes metastasis of gastric cancer cells by upregulating IGF-2, by X.-Y. Wu, H.-Y. Zhou, X.-M. Yao, X.-D. Chen, J. Wu, X.-C. Lu, published in Eur Rev Med Pharmacol Sci 2020; 24 (1): 145-150-DOI: 10.26355/eurrev_202001_19905-PMID: 31957827" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19905.

LncRNA LINP1 promotes proliferation and inhibits apoptosis of gastric cancer cells by repressing RBM5.

OBJECTIVE: Recent studies have revealed that long non-coding RNAs (lncRNAs) play a crucial role in tumor progression. Gastric cancer (GC) is one of the common types of malignancies worldwide. This study aimed to identify the exact function of lncRNA LINP1 in the progression of GC. PATIENTS AND METHODS: LINP1 expression in paired cancer tissues and adjacent normal tissues of GC patients was detected by Real-Time quantitative Polymerase Chain Reaction (RT-qPCR). The effect of LINP1 silence on proliferation and apoptosis of GC cells was detected. Meanwhile, the underlying mechanism of LINP1 function was explored by RT-qPCR and Western blot assay. Furthermore, tumor formation assay was performed to examine the ability of LINP1 in tumor formation in vivo. RESULTS: LINP1 expression was remarkably up-regulated in GC tissues compared with adjacent normal tissues. The growth ability of GC cells was significantly inhibited after silencing of LINP1 in vitro. Besides, the apoptosis of GC cells was markedly induced after silencing of LINP1. The silence of LINP1 significantly up-regulated the expression of RBM5 in GC cells. Meanwhile, RBM5 expression in GC tissues was remarkably lower than that of the adjacent normal tissues. Furthermore, tumor formation assay showed that knockdown of LINP1 markedly inhibited tumor formation in vivo. CONCLUSIONS: These results suggested that LINP1 could down-regulate RBM5. Meanwhile, LINP1 remarkably promoted growth ability and suppressed apoptosis of GC in vitro and in vivo. Our findings might provide a novel regulator and therapeutic strategy for GC patients.

Long non-coding RNA AB073614 promotes metastasis of gastric cancer cells by upregulating IGF-2.

OBJECTIVE: Recently, long non-coding RNAs (lncRNAs) have been widely studied for their vital roles in human diseases. In this study, we investigated the effect of lncRNA AB073614 on the metastasis of gastric cancer (GC), and explored the possible underlying mechanism. PATIENTS AND METHODS: AB073614 expression in GC tissue samples was detected by Real-time quantitative polymerase chain reaction (RT-qPCR). The roles of AB073614 in GC metastasis were identified through wound healing assay and transwell assay, respectively. Moreover, RT-qPCR and Western blot assay were used to explore the potential mechanism. RESULTS: AB073614 expression level in GC samples was significantly higher than that of adjacent ones. Besides, the migration and invasion of GC cells were obviously repressed after AB073614 was knocked down. After AB073614 was knocked down in vitro, the mRNA and protein expressions of insulin-like growth factor 2 (IGF-2) was remarkably down-regulated. Furthermore, a negative correlation was found between the expression level of IGF-2 and AB073614 in GC tissues. CONCLUSIONS: AB073614 could promote GC cell migration and invasion via up-regulating IGF-2. Our findings might provide a potential therapeutic target for GC patients.

Modeling cerebral ischemia in neuroproteomics.

Protein changes induced by traumatic or ischemic brain injury can serve as diagnostic markers as well as therapeutic targets for neuroprotection. The focus of this chapter is to provide a representative overview of preclinical brain injury and proteomics analysis protocols for evaluation and discovery of novel biomarkers. Detailed surgical procedures have been provided for inducing MCAo and implantation of chronic indwelling cannulas for drug delivery. Sample collection and tissue processing techniques for collection of blood, CSF, and brain are also described including standard biochemical methodology for the proteomic analysis of these tissues.The dynamics of proteomic analysis is a multistep process comprising sample preparation, separation, quantification, and identification of proteins. Our approach is to separate proteins first by two-dimensional gel electrophoresis according to charge and molecular mass. Proteins are then fragmented and analyzed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Identification of proteins can be achieved by comparing the mass-to-charge data to protein sequences in respective databases.

[Effect of comprehensive AIDS intervention among men aged 50 or over who had non-marital sexual behavior].

Objective: To evaluate the effectiveness of AIDS intervention programs on men aged 50 or over and having had non-marital sexual behavior. Methods: A community-based intervention/experimental and based on individual level study was adopted. Stratified sampling method was used. 12 townships/streets in Fuyang district of Hangzhou were identified as intervention or control group (six research sites each). All of the subjects in the township (street) were included. The inclusion criteria of study objects would include men aged 50 or older who reported having unmarried sex in the last year. Estimated sample size was 290, with each 145 in the intervention group and the control group. All the intervention group participants were provided with a total of 4 intervention-related items (knowledge and education on AIDS prevention, information radiation and behavioral change, broadcast expert lectures), every 3 months, for 12 month, the main evaluation indicators would include: incidence of non-marital sex and commercial sex in the last year, condom use when having non-marital sex in the last episode. Results: A total of 312 subjects were recruited. 300 of them completed the baseline study while 284 of them completed the follow-up survey. Among the subjects who had undergone the baseline study, the average age was (65.58±7.89), 71.33% were married or cohabiting with someone, 52.00% having had primary school education. After the implementation of intervention programs, the incidence of non-marital sex dropped to 59.42% (82/138) and the incidence of commercial sex dropped from 79.73% (118/148) to 55.07% (76/138). Condom use rate in the last non-marital sexual contact increased from 19.59% (29/148) to 51.22% (42/82). In the control group, the incidence of non-marital sex in the year before dropped to 74.66% (109/146) and the incidence of commercial sex dropped from 91.45% (139/152) to 72.60% (106/146). Rates of condom use during the last non-marital sexual contact dropped from 32.89% (50/152) to 31.19% (34/109). Statistically, there were significant differences appeared between the two groups on the incidence of non-marital sex in the past year (χ(2)=7.48, P=0.008), the incidence of commercial sex in the last year (χ(2)=9.47, P=0.003) and the rate of condom use in the last sex experience (χ(2)=7.83, P=0.007). Conclusions: Results from this intervention study showed that: in the intervention group, both the incidence rates of non-marital or commercial sex had reduced, together with the increase of condom use in non-marital sex in the last sexual experience. Intervention strategies that involving knowledge and education on AIDS prevention, information radiation and behavioral change, broadcasting lectures by experts etc. were all proved effective.

Daylength responses of various morphogenetic events after panicle initiation in late japonica rice (Oryza sativa L. ssp. japonica).

Plant morphogenesis is an intimate cooperation between environmental signals and a genetically-encoded developmental programme. Although all stages subsequent to floral induction may be influenced by daylength, the information available has come from diverse species during different morphogenetic events. This makes it difficult to investigate how photoperiodic signalling is integrated into various steps of the developmental programme. Here, we report that, in late japonica rice lines, morphogenetic events, including 12th leaf, axis of the main panicle, awn of the glum, anthers, elongation rate of internodes, and pollen fertility of the photoperiod-sensitive genic male-sterile (PGMS) rice, are significantly affected by daylength after panicle initiation. These data indicate that daylength affects many morphologic events, and that changes in morphology are mainly determined by the characteristics of the events themselves. These findings lay a foundation for future investigations into how potentially common photoperiodic signalling system(s) are integrated with diversified developmental events. In addition, we discussed the essential nature of PGMS rice.

Detection of protein biomarkers using high-throughput immunoblotting following focal ischemic or penetrating ballistic-like brain injuries in rats.

PRIMARY OBJECTIVE: Recent efforts have been aimed at developing a panel of protein biomarkers for the diagnosis/prognosis of the neurological damage associated with acute brain injury. METHODS AND PROCEDURES: This study utilized high-throughput immunoblotting (HTPI) technology to compare changes between two animal models of acute brain injury: penetrating ballistic-like brain injury (PBBI) which mimics the injury created by a gunshot wound and transient middle cerebral artery occlusion (MCAo) which is a model of stroke. Brain and blood were collected at 24-hours post-injury. MAIN OUTCOMES AND RESULTS: This study identified the changes in 18 proteins following PBBI and 17 proteins following MCAo out of a total of 998 screened proteins. Distinct differences were observed between the two models: five proteins were up- or down-regulated in both models, 23 proteins changed in only one model and one protein was differentially expressed. Western blots were used to verify HTPI results for selected proteins with measurable changes observed in both blood and brain for the proteins STAT3, Tau, PKA RII beta, 14-3-3 epsilon and p43/EMAPII. CONCLUSIONS: These results suggest distinct post-injury protein profiles between brain injury types (traumatic vs. ischemic) that will facilitate strategies aimed at the differential diagnosis and prognosis of acute brain injury.

Long noncoding RNA LINC00265 predicts the prognosis of acute myeloid leukemia patients and functions as a promoter by activating PI3K-AKT pathway.

OBJECTIVE: Mounting evidence suggests that long noncoding RNAs (lncRNAs) function in multiple cancers. This study aimed to determine the expression, clinical significance, and possible biological function of a novel lncRNA LINC00265 in acute myeloid leukemia (AML). PATIENTS AND METHODS: The expression levels of LINC00265 were systematically evaluated in TCGA datasets. RT-PCR was performed to examine the expression level of LINC00265 in bone marrow and serum obtained from AML patients and healthy controls. The clinical data were interpreted by x2 test, Kaplan-Meier analyses, univariate analysis, and multivariate analysis. The functional role of LINC00265 was verified using cell experiments. Western blotting was used to examine the modulatory effect of LINC00265 on AKT/PI3K pathway in AML. RESULTS: LINC00265 was significantly highly expressed in the bone marrow and serum of AML patients. High serum LINC00265 was significantly associated with FAB classification and cytogenetics. ROC analyses showed that serum LINC00265 levels were reliable in distinguishing patients with AML from normal controls. Clinical assay indicated that AML patients with higher serum LINC00265 expression suffered poorer overall survival. Functionally, overexpression of LINC00265 suppressed the capability of proliferation, migration and invasion in AML cell lines. By using Western blot, we further illustrated that LINC00265 activated PI3K/AKT signaling in AML cell lines. CONCLUSIONS: Our findings not only demonstrated that LINC00265 contributes to AML proliferation, migration and invasion via modulation of PI3K/AKT signaling, but also suggested the potential value of LINC00265 as a clinical prognostic and a diagnostic marker for AML.

[Gene expression profile analysis involved in pathogenesis of allergic rhinitis by using bioinformatics method as a novel way of drug screening].

Objective: To analyze the dynamic changes of the clinical features of chronic rhinosinusitis in recent 10 years, so as to deeply understand the characteristics of chronic rhinosinusitis, and to provide new ideas for treatment of chronic rhinosinusitis. Method: This retrospective study was performed in patients who were diagnosed as chronic rhinosinusitis and enrolled. General information, clinical examination and pathological results were all collected, then patients' age, gender, the incidence of asthma and allergic rhinitis, peripheral eosinophil percentage, olfactory dysfunction and pathological results were statistically analyzed. Result: 1 955 patients who were diagnosed as chronic rhinosinusitis(CRS) were enrolled in this study, including 570 patients in 2006, 583 patients in 2010, and 802 patients in 2015. There were no obvious changes of age structure in these patients in three years. And there was no significant change in sex ratio as well. The proportions of patients with CRS concomitant with asthma were obviously increased in 10 years, which was 3.51% in 2006, 7.55% in 2010, and 17.58% in 2015. The proportions of patients with allergic rhinitis were also increased, which was 10.35% in 2006, 8.75% in 2010, and 14.09% in 2015. Peripheral eosinophil ratio was increased significantly in these patients after 2010. The proportions of ECRS in CRS were elevated in 2015 and almost doubled compared to 2006. Olfactory dysfunction increased significantly in 2015. Conclusion: In recent 10 years, there were obvious changes of clinical features of CRS. The proportion of patients with CRS concomitant with asthma showed a gradual increasing trend. ECRS significantly increased than it was 10 years ago. Olfactory dysfunction also increased significantly. In order to improve the therapeutic effect of CRS, it is necessary to strengthen the treatment of upper and lower airway inflammation related with eosinophil.

PAN-811 provides neuroprotection against glutamate toxicity by suppressing activation of JNK and p38 MAPK.

In an earlier study, we demonstrated that PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel neuroprotectant, provides protection against glutamate, staurosporine, veratridine, or hypoxia/hypoglycemia toxicities in primary cortical neuronal cultures by upregulating Bcl-2 expression [R.-W. Chen, C. Yao, X.C. Lu, Z.-G. Jiang, R. Whipple, Z. Liao, H.A. Ghanbari, B. Almassian, F.C. Tortella, J.R. Dave. PAN-811 (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), a novel neuroprotectant, elicits its function in primary neuronal cultures by upregulating Bcl-2 expression. Neuroscience 135 (2005) 191-201]. Both JNK (c-Jun N-terminal kinase) and p38 MAP (mitogen-activated protein) kinase activation have a direct inhibitory action on Bcl-2 by phosphorylation. In the present study, we continued to explore the mechanism of PAN-811 neuroprotection. Our results indicate that treatment of cultured cortical neurons with glutamate (100 microM) induces phosphorylation of both JNK and p38 MAPK. Specifically, pretreatment of neurons with 10 microM PAN-811 (an optimal neuroprotective concentration) for 1h, 4h, or 24h significantly suppresses glutamate-mediated activation of both JNK and p38 MAPK. Furthermore, the p38 MAPK-specific inhibitor SB203580 and the JNK-specific inhibitor SP600125 prevented glutamate-induced neuronal death in these primary cultures. Our results demonstrate that glutamate-induced phosphorylation of JNK and p38 MAPK is suppressed by PAN-811, which might contribute to Bcl-2 upregulation and PAN-811 neuroprotection.

MiR-222 promotes proliferation, migration and invasion of lung adenocarcinoma cells by targeting ETS1.

OBJECTIVE: The lung adenocarcinoma is a type of lung cancer. This research is to investigate the effects of miR-222 on the proliferation, migration and invasion of the lung adenocarcinoma cells. MATERIALS AND METHODS: At the beginning, MiR-222 and the controls were transfected to the lung adenocarcinoma cell line A549 for CCK-8 proliferation, transwell migration and Matrigel invasion, and then observed the effect of miR-222 on the proliferation, migration and invasion of lung adenocarcinoma cells. The miR-222 target was regulated by ETS1 downwards to participate in the regulation of the process by using the luciferase reporter assay, the Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and the Western blotting. RESULTS: According to CCK-8 proliferation assay, the Transwell migration and the Matrigel invasion assay, it discovered that MiR-222 can promote the proliferation, migration and invasion of the lung adenocarcinoma cells. Luciferase reporter assay, RT-qPCR and Western blot assay showed that miR-222 could regulate the expression of ETS1 downwards and ETS1 participated in the regulation of the process CONCLUSIONS: ETS1 promotes proliferation, migration and invasion of lung adenocarcinoma cells by targeting the regulated miR-222 downwards.

Statin-treated patients with aneurysmal subarachnoid haemorrhage: a meta-analysis.

OBJECTIVE: The cerebral vasospasm, delayed ischemic neurological deficit (DIND), mortality and poor neurological outcome induced by aneurysmal subarachnoid haemorrhage (SAH) remain the major causes of morbidity and mortality in aneurysmal SAH patients. The effects of statin-treated for aneurysmal SAH patients were not comprehensively assessed. PATIENTS AND METHODS: A systematically literature search was conducted in PubMed, EMBASE, ScienceDirect and Web of Science to identify relevant studies update to March 2015. Data were extracted and appraised independently by two authors. Moreover, fixed or random effects models were applied to calculate pooled results based on the degree of heterogeneity. RESULT: Nine RCTs and three observational studies with a total of 1957 patients met the inclusion criteria. The results showed that statin treatment was not associated with a decrease in the occurrence of DIND (RR: 0.81, 95% CI: 0.66-1.00, p = 0.05), mortality (RR: 0.90, 95% CI: 0.69-1.18, p = 0.46) and poor neurological outcome (RR: 1.02, 95% CI: 0.86-1.20, p = 0.84), nonetheless, had a potential effect on reducing the incidence of vasospasm (RR: 0.77, 95% CI: 0.66-0.89, p = 0.0006). CONCLUSIONS: This meta-analysis indicated that the use of statins decreases the occurrence of cerebral vasospasm, whereas did not support a beneficial effect of statins on the occurrence of DIND, death or poor neurological outcomes in patients with aneurysmal SAH.

Delayed secondary phase of peri-infarct depolarizations after focal cerebral ischemia: relation to infarct growth and neuroprotection.

In focal cerebral ischemia, peri-infarct depolarizations (PIDs) cause an expansion of core-infarcted tissue into adjacent penumbral regions of reversible injury and have been shown to occur through 6 hr after injury. However, infarct maturation proceeds through 24 hr. Therefore, we studied PID occurrence through 72 hr after both transient and permanent middle cerebral artery occlusion (MCAo) via continuous DC recordings in nonanesthetized rats. PIDs occurred an average 13 times before reperfusion at 2 hr and then ceased for an average approximately 8 hr. After this quiescent period, PID activity re-emerged in a secondary phase, which reached peak incidence at 13 hr and consisted of a mean 52 PIDs over 2-24 hr. This phase corresponded to the period of infarct maturation; rates of infarct growth through 24 hr coincided with changes in PID frequency and peaked at 13 hr. In permanent MCAo, PIDs also occurred in a biphasic pattern with a mean of 78 events over 2-24 hr. Parameters of secondary phase PID incidence correlated with infarct volumes in transient and permanent ischemia models. The role of secondary phase PIDs in infarct development was further investigated in transient MCAo by treating rats with a high-affinity NMDA receptor antagonist at 8 hr after injury, which reduced post-treatment PID incidence by 57% and provided 37% neuroprotection. Topographic mapping with multielectrode recordings revealed multiple sources of PID initiation and patterns of propagation. These results suggest that PIDs contribute to the recruitment of penumbral tissue into the infarct core even after the restoration of blood flow and throughout the period of infarct maturation.

Mechanism of transcriptional regulation of LRP16 gene expression by 17-beta estradiol in MCF-7 human breast cancer cells.

LRP16 gene expression is induced by 17-betaestradiol (E2) via estrogen receptor alpha (ERalpha) in MCF-7 human breast cancer cells. A previous study also demonstrated that ectopic expression of LRP16 gene promoted MCF-7 cell proliferation. To explore the mechanism of hormone-induced LRP16 gene expression, the LRP16 gene promoter region (-2600 to -24 bp upstream of the LRP16 gene translation starting site) was analyzed in the present study by using different 5'-truncated constructs, and a luciferase reporter. The 5'-flanking sequence of -676 to -24 bp (pGL3-S5) was found to be E2-responsive. After exchange of the fragment from -213 to -24 bp with the TK gene proximal promoter region in pGL3-S5, E2 still induced reporter gene activity in MCF-7 and HeLa cells. Sequence analysis showed that the pGL3-S6 (-676 to -214) sequence contains two motifs that may contribute to E2-induced transactivation; namely, an estrogen-responsive element (ERE) half-site/Sp1 at -246 to -227 bp and an E-box site at -225 to -219 bp. Further deletion and mutation analysis of these two motifs indicated that both the 1/2 ERE and Sp1 binding sites were required for E2 action, while E-box deletion did not affect the luciferase activity in MCF-7 and HeLa cells. The results of gel mobility shift and chromatin immunoprecipitation assays confirmed that both ERalphaand Sp1 were required for hormone-induced transactivation, which involved both ERalphaand Sp1 directly binding to DNA. Taken together, these findings suggest that ERalphaand Sp1 play a role in activation of the human LRP16 gene promoter.