Helicid Alleviates Neuronal Apoptosis of Rats with Depression-Like Behaviors by Downregulating lncRNA-NONRATT030918.2.

Helicid (HEL) has been found to possess antidepressant pharmacological activity. The paper was to testify to the precise molecular mechanism through which HEL regulates lncRNA-NONRATT030918.2 to exert an antidepressant impression in depression models. A depression model stimulated using chronic unpredictable mild stress (CUMS) was created in rats, and the depressive state of the rats was assessed through behavioral experiments. Additionally, an in vitro model of PC12 cells induced by corticosterone (CORT) was established, and cytoactive was tested using the CCK8. The subcellular localization of the NONRATT030918.2 molecule was confirmed through a fluorescence in situ hybridization experiment. The relationship between NONRATT030918.2, miRNA-128-3p, and Prim1 was analyzed using dual-luciferase reporter gene assay, RNA Binding Protein Immunoprecipitation assay, and RNA pull-down assay. The levels of NONRATT030918.2, miRNA-128-3p, and Prim1 were tested using Q-PCR. Furthermore, the levels of Prim1, Bax, Bcl-2, and caspase3 were checked through Western blot. The HEL can alleviate the depression-like behavior of CUMS rats (P < 0.05), and reduce the mortality of hippocampal via downregulating the level of NONRATT030918.2 (P < 0.05). In CORT-induced PC12 cells, intervention with HEL led to decreased expression of NONRATT030918.2 and Prim1 (P < 0.05), as well as increased expression of miRNA-128-3p (P < 0.05). This suggests that HEL regulates the expression of NONRATT030918.2 to upregulate miRNA-128-3p (P < 0.05), which in turn inhibits CORT-induced apoptosis in PC12 cells by targeting Prim1 (P < 0.05). The NONRATT030918.2/miRNA-128-3p/Prim1 axis could potentially serve as a crucial regulatory network for HEL to exert its neuroprotective effects.

Poria cocos Attenuated DSS-Induced Ulcerative Colitis via NF-κB Signaling Pathway and Regulating Gut Microbiota.

Ulcerative colitis (UC), as a chronic inflammatory disease, presents a global public health threat. However, the mechanism of Poria cocos (PC) in treating UC remains unclear. Here, LC-MS/MS was carried out to identify the components of PC. The protective effect of PC against UC was evaluated by disease activity index (DAI), colon length and histological analysis in dextran sulfate sodium (DSS)-induced UC mice. ELISA, qPCR, and Western blot tests were conducted to assess the inflammatory state. Western blotting and immunohistochemistry techniques were employed to evaluate the expression of tight junction proteins. The sequencing of 16S rRNA was utilized for the analysis of gut microbiota regulation. The results showed that a total of fifty-two nutrients and active components were identified in PC. After treatment, PC significantly alleviated UC-associated symptoms including body weight loss, shortened colon, an increase in DAI score, histopathologic lesions. PC also reduced the levels of inflammatory cytokines TNF-α, IL-6, and IL-1ß, as evidenced by the suppressed NF-κB pathway, restored the tight junction proteins ZO-1 and Claudin-1 in the colon, and promoted the diversity and abundance of beneficial gut microbiota. Collectively, these findings suggest that PC ameliorates colitis symptoms through the reduction in NF-κB signaling activation to mitigate inflammatory damage, thus repairing the intestinal barrier, and regulating the gut microbiota.

Flexible Three-Dimensional Force Tactile Sensor Based on Velostat Piezoresistive Films.

The development of a high-performance, low-cost, and simply fabricated flexible three-dimensional (3D) force sensor is essential for the future development of electronic skins suitable for the detection of normal and shear forces for several human motions. In this study, a sandwich-structured flexible 3D force tactile sensor based on a polyethylene-carbon composite material (velostat) is presented. The sensor has a large measuring range, namely, 0-12 N in the direction of the normal force and 0-2.6 N in the direction of the shear force. For normal forces, the sensitivity is 0.775 N-1 at 0-1 N, 0.107 N-1 between 1 and 3 N, and 0.003 N-1 at 3 N and above. For shear forces, the measured sensitivity is 0.122 and 0.12 N-1 in x- and y-directions, respectively. Additionally, the sensor exhibits good repeatability and stability after 2500 cycles of loading and releasing. The response and recovery times of the sensor are as fast as 40 and 80 ms, respectively. Furthermore, we prepared a glove-like sensor array. When grasping the object using the tactile glove, the information about the force applied to the sensing unit can be transmitted through a wireless system in real-time and displayed on a personal computer (PC). The prepared flexible 3D force sensor shows broad application prospects in the field of smart wearable devices.

NLRP3/miR-223-3p axis attenuates neuroinflammation induced by chronic intermittent hypoxia.

Obstructive sleep apnea (OSA) is mainly characterized by chronic intermittent hypoxia (CIH) with multiple brain injuries. Nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome is considered the most important factor inducing and maintaining inflammation. However, the role of NLRP3 and its underlying mechanism in CIH-elicited neuroinflammation remains unclear. We constructed an OSA-related CIH in vivo model and assessed the rats' cognitive behavior in the Morris water maze. The combination of miR-223-3p and NLRP3 was confirmed by the TargetScan database, double luciferase reporter gene experiment, and RNA immunoprecipitation (RIP) experiment. Western blot and ELISA assay were used to analyze the effects of miR-223-3p targeting NLRP3 on the expression of pyroptotic or inflammatory factors in vivo in CIH rats. Severe cognitive impairment was observed in rats at week 6 post-treatment, with increased inflammatory factors in the blood and hippocampus, heightened NLRP3 expression, and low miR-223-3p levels. And the good binding activity of the two was confirmed by dual luciferase reporter and RIP experiments. Next, we found that silencing NLRP3 or overexpression of miR-223-3p in the CIH model could improve cognitive deficits and reduce the level of proinflammatory factors and pyroptosis factors in rats. Finally, based on silencing NLRP3 or overexpression miR-223-3p, we confirmed that there was a regulatory relationship between miR-223-3p and NLRP3. Our results suggested that the NLRP3/ miR-223-3p axis played a role in attenuating CIH-induced neuroinflammation.

Ultra-High Cycling Stability of 3D Flower-like Ce(COOH)3 for Supercapacitor Electrode via a Facile and Scalable Strategy.

An electrode material with high performance, long durability, and low cost for supercapacitors has long been desired in academia and industry. Among all the factors that affect the electrochemical performance and cycling stability of electrode materials, the morphology and intrinsic structure characteristics are the most important. In this study, a novel 3D flower-like Ce(COOH)3 electrode material was designed by taking advantage of the Ce3+ and -COOH groups and fabricated by a one-pot microwave-assisted method. The morphology and structure characteristics of the sample were examined by SEM, EDS, TEM, XRD, FT-IR, XPS, N2 adsorption/desorption techniques, and the electrochemical behaviors were investigated in a three-electrode configuration. The Ce(COOH)3 electrode presents an excellent specific capacitance of 140 F g-1 at 1 A g-1, higher than many other previously reported Ce-based electrodes. In addition, it delivers high rate capability that retains 60% of its initial capacitance when the current density is magnified 20 times. Dramatically, the Ce(COOH)3 electrode exhibits an ultra-high cycling stability with capacitance retention of 107.9% after 60,000 cycles, which is the highest durability among reported Ce-organic compound electrodes to the best of our knowledge. The excellent electrochemical performance is ascribed to its intrinsic crystal structure and unique morphology. This work indicates that the 3D flower-like Ce(COOH)3 has significant potential for supercapacitor applications and the facile and scalable synthesis strategy can be extended to produce other metal-organic composite electrodes.

PDC-Net: parallel dilated convolutional network with channel attention mechanism for pituitary adenoma segmentation.

Accurate segmentation of the medical image is the basis and premise of intelligent diagnosis and treatment, which has a wide range of clinical application value. However, the robustness and effectiveness of medical image segmentation algorithms remains a challenging subject due to the unbalanced categories, blurred boundaries, highly variable anatomical structures and lack of training samples. For this reason, we present a parallel dilated convolutional network (PDC-Net) to address the pituitary adenoma segmentation in magnetic resonance imaging images. Firstly, the standard convolution block in U-Net is replaced by a basic convolution operation and a parallel dilated convolutional module (PDCM), to extract the multi-level feature information of different dilations. Furthermore, the channel attention mechanism (CAM) is integrated to enhance the ability of the network to distinguish between lesions and non-lesions in pituitary adenoma. Then, we introduce residual connections at each layer of the encoder-decoder, which can solve the problem of gradient disappearance and network performance degradation caused by network deepening. Finally, we employ the dice loss to deal with the class imbalance problem in samples. By testing on the self-established patient dataset from Quzhou People's Hospital, the experiment achieves 90.92% of Sensitivity, 99.68% of Specificity, 88.45% of Dice value and 79.43% of Intersection over Union (IoU).

Effect of Grain Structure and Ni/Au-UBM Layer on Electromigration-Induced Failure Mechanism in Sn-3.0Ag-0.5Cu Solder Joints.

The development of advanced electronic devices leads to highly miniaturized interconnect circuits (ICs), which significantly increases the electromigration (EM) phenomenon of solder and circuits due to higher current density. The electromigration of solder joints under high current density has become a severe reliability concern in terms of microelectronic product reliability. The microstructure of the solder plays an important role in the electromigration induced degradation. In this study, Sn-3.0Ag-0.5Cu solder bumps with Ni/Au under bump metallization (UBM) layer were fabricated and electromigration acceleration tests were conducted under current density of 1.4 × 104 A/cm2 and 120 °C to investigate the effect of grain structure and Ni/Au-UBM layer on EM-induced failure. Grain structures of solder bumps were determined by utilizing the Electron Backscatter Diffraction (EBSD) technique, and single-crystal solder, single-crystal dominated solder, and polycrystalline solder are observed in different test samples. According to the Scanning Electron Microscope (SEM) images, it is observed that the Ni/Au-UBM layer of the Cu pad can inhibit atom diffusion between solder bump and Cu pad, which reduces the consumption of Cu pad but causes a large void and crack at the interface. The EM lifetime of single crystal solder bumps is lower than that of polycrystalline solder bumps when the c-axis of single crystal solder bumps is perpendicular to the electron flow direction. Additionally, the single crystal structure will increase the brittleness of the solder bump, and cracks are easily generated and expanded under the stress caused by the mismatch of thermal expansion coefficients between the solder bump and Ni/Au-UBM layer near Cu pad. Polycrystalline solder bumps with a higher misorientation angle (15-55°) have a higher atom diffusion rate, which will result in the acceleration of the EM-induced failure.

Helicid Improves Lipopolysaccharide-Induced Apoptosis of C6 Cells by Regulating SH2D5 DNA Methylation via the CytC/Caspase9/Caspase3 Signaling Pathway.

DNA methylation is reportedly associated with stress responses and depression. Treatment with antidepressants can regulate DNA methylation and, subsequently, gene expression in the hippocampus. Hence, DNA methylation is a potential target for treatment of depression. Screening of high-throughput data of a rat model of chronic unpredictable mild stress revealed relatively low expression of SH2 domain-containing 5 (SH2D5). SH2D5 can be overexpressed by treatment with helicid. Therefore, in order to further explore the role of SH2D5 in depression and whether helicid mediates the DNA methylation of SH2D5 as a potential antidepressant role, SH2D5 was overexpressed in C6 cells as a lipopolysaccharides (LPS)-induced model of depression. The expression levels of Bax, Bcl-2, Bad, and Daxx, and changes to the CytC/caspase9/caspase3 signal pathway were detected by qRT-PCR and Western blot analyses. After treatment with helicid or silencing of SH2D5, the above indices were detected. The results showed that helicid regulated the CytC/caspase9/caspase3 signaling pathway and improved the apoptosis indices of C6 cells through the overexpression of SH2D5. Interestingly, silencing of SH2D5 reversed the effects of helicid on the above indices. Then, in order to study the underlying mechanism, the cells were administered to helicid or 5-aza-2'-deoxycytidine (5-AzaD) and expression of SH2D5 was detected by qRT-PCR and Western blot analyses, while to assess the DNA methylation level of SH2D5 using bisulfite sequencing/PCR. The results showed that SH2D5 was hypermethylated with low expression in LPS-induced C6 cells, which was reversed by helicid and 5-AzaD. These results suggest that helicid may affect the CytC/caspase9/caspase3 apoptosis signaling pathway and improve the apoptosis indices by mediating DNA methylation of SH2D5.

Helicid Reverses the Effect of Overexpressing NCALD, Which Blocks the sGC/cGMP/PKG Signaling Pathway in the CUMS-Induced Rat Model.

Background: Increasing evidence has shown that apoptosis in the hippocampus is closely related to depressive-like behavior. We previously reported that helicid had good antidepressant activities, which manifested as the alleviation of depression-like behaviors and the reversal of the high expression of neurocalcin delta (NCALD) in chronic unpredictable mild stress (CUMS) rats. The aim of this study was, therefore, to characterize the antidepressant-like effects and underlying mechanism of helicid on CUMS rats by silencing NCALD and using rescue experiments. Methods: We developed the CUMS rat model using CUMS stimulation from week 0 to week 6. The rats were treated with helicid, or NCALD silenced, then we overexpressed NCALD using adeno-associated virus. We also measured the protein levels of sGCα1, sGCß1, PKG1/2, and cleaved caspase-3 in hippocampal tissues using western blotting and measured cGMP using an ELISA. Results: Treating CUMS rats by silencing NCALD or by the administration of helicid improved the depressive-like behavior. The levels of proteins, including sGC, PKG, cleaved caspase-3, and cGMP, in hippocampus all decreased. NCALD overexpression reversed these decreases and reversed the alleviation of depression-like behaviors in CUMS rats. Limitation. We only detected the antidepressant effects of helicid in the hippocampus; therefore, other parts of brain should also be studied. Conclusions: Inhibition of NCALD, as well as helicid administration, alleviated antidepressant-like behavior by regulating the expressions of apoptotic cytokines and the sGC/cGMP/PKG signaling pathway. Overexpressing NCALD reversed the amelioration effects of silenced NCALD and helicid administration.

Evolution of the Shear Band in Cold-Rolling of Strip-Cast Fe-1.3% Si Non-Oriented Silicon Steel.

Cube texture and microstructural evolution of as-cast non-oriented silicon steel (1.3% Si) during cold rolling and annealing were studied. The results showed that the as-cast microstructure with grain size in the range of 100-500 µm had a weak texture. The strong orientation was mainly located at {100} and {110} planes. A significant content of shear-deformed grains oriented with {110}<110> were obtained by cold-rolling, and many regions oriented with Cube texture were distributed in the shear bands. During cold-rolling, the orientation of the shear-deformed microstructure tilted towards the {111}<112> orientation, while the matrix orientation retained {110}<110>. On further cold-rolling, the residual part of {110}<110> experienced shear deformation, forming more shear bands, strengthening the Cube orientation. During annealing, Cube orientation grains nucleated in the shear bands leading to strong Cube texture, and corresponding B50 was 1.83T/1.79T.

Antidepressant-like effects of helicid on a chronic unpredictable mild stress-induced depression rat model: Inhibiting the IKK/IκBα/NF-κB pathway through NCALD to reduce inflammation.

We previously reported that helicid, an active plant monomer of Helicid nilgirica Bedd, had good antidepressant pharmacological activities. However, the potential mechanism of action remains unknown. Current investigation showed the antidepressant-like effects of helicid and its effects on the neurocalcin delta (NCALD) gene, and its mechanism of action through a depression model in rats exposed to chronic unpredictable mild stress (CUMS). We evaluated depression symptoms using the sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST). By silencing NCALD and using rescue experiments, the IL-6, iNOS, IL-1ß, COX-2, and TNF-α levels in the hippocampus or peripheral blood were determined using western blotting and ELISAs. The expression of IKKß, p-IкBα, p-IKKß, NF-кB p65, and IкBα were tested using western blots of the cytoplasmic or nuclear samples. Helicid and silencing NCALD relieved the CUMS-irritated depressive-like actions of rats, which were shown by increased consumption of sucrose, numbers of rearings, total running distance, zone crossings, and reduced immobility times. Helicid or silencing NCALD reversed the CUMS-induced high levels of IL-1ß, COX-2, IL-6, TNF-α, and iNOS in the hippocampus or peripheral blood. Helicid or silencing NCALD also reduced the expressions of p-IκBα and p-IKKß in the cytoplasm and the expression of nuclear NF-κB p 65 in hippocampus, and simultaneously elevated cytoplasmic expressions of IκBα, IKKß, and NF-κB p65 in the hippocampus. Notably, after NCALD overexpression, the biochemical indices of rat helicid administration were reversed. In conclusion, the antidepressant action of helicid was mediated through NCALD in rats of CUMS by repressing hippocampal neuro-inflammation and abating the activation of the IKK/IκBα/NF-κB pathway.

Preliminary comparison of the efficacy of several surgical treatments based on maxillomandibular advancement procedures in adult patients with obstructive sleep apnoea: a systematic review and network meta-analysis.

PURPOSE: To evaluate the efficacy of eight different surgical treatments based on maxillomandibular advancement (MMA), which has emerged in recent years, for adult obstructive sleep apnoea (OSA) patients. METHODS: The literature was searched from January 2010 to May 2020 for studies of adult OSA patients with different types of MMA procedures to perform a network meta-analysis. The outcomes were changes in the apnoea-hypopnoea index (AHI), the lowest pulse oxygen saturation (SpO2 min) and the Epworth Sleepiness Scale (ESS). Treatment hierarchy was summarized according to the rank charts. RESULTS: Eight studies were included and encompassed a total of 227 adult patients diagnosed with OSA. Among them, 225 patients underwent combined surgery or simple MMA surgery, including modified maxillomandibular advancement (MMMA),counterclockwise maxillomandibular advancement (CMMA), drug-induced sleep endoscopy and maxillomandibular advancement (MMA + DISE), transoral robotic surgery and maxillomandibular advancement (MMA + TORS), uvulopalatopharyngoplasty (UPPP), maxillomandibular advancement and uvulopalatopharyngoplasty (MMA + UPPP), uvulopalatopharyngoplasty with uvula preservation and maxillomandibular advancement (MMA + HUPPP); MMA consisting of Le Fort I osteotomy and bilateral inverted-L osteotomy (ILOs), genioplasty and iliac bone grafting; and MMA consisting of Le Fort I osteotomy, bilateral sagittal split ramus osteotomies and genioplasty. The results showed that the most effective surgical treatment is MMA + HUPPP [- 56.79 (WMD); 95% confidence interval (CI): - 113.02 to - 3.33] (P < 0.00001), which was far superior to other approaches. CONCLUSION: MMA combined with HUPPP had the highest efficacy. The MMA consisted of Le Fort I osteotomy, bilateral sagittal split ramus osteotomies and genioplasty; CMMA and MMA + TORS are likely also great choices.

Comparative HPLC-MS/MS-based pharmacokinetic studies of multiple diterpenoid alkaloids following the administration of Zhenwu Tang and Radix Aconiti Lateralis Praeparata extracts to rats.

Abstracts Zhenwu Tang (ZWT) is a traditional Chinese medicine that is primarily composed of Radix Aconiti Lateralis Praeparata (FZ) and diterpenoid alkaloids are believed to be the pharmacologically active compounds of ZWT. In this study, the pharmacokinetic profiles of hypaconitine, mesaconitine, aconitine, benzoylmesaconitine, benzoylaconitine, and benzoylhypacoitine were assessed in rats following intragastric ZWT administration. Furthermore, differences in the pharmacokinetic profiles of these six alkaloids were assessed as a function of rat sex and the administration of ZWT or FZ extracts to these animals. Plasma levels of these alkaloids were quantified via HPLC-MS/MS. Significant differences in key pharmacokinetic parameters were observed when comparing rats administered FZ or ZWT. Relative to FZ extract treatment, ZWT administration was associated with Cmax and AUC0-∞ values of benzoylmesaconitine that were about 3.5 and 5.5 times higher. Considerable variations in hypaconitine pharmacokinetic parameters were also revealed between female and male rats. The Cmax and AUC0-∞ of hypaconitine were about 2.5- and 2.7-fold elevated in female rats in comparison with male rats. These results suggested that the other compounds within ZWT can enhance the absorption of benzoylmesaconitine, while hypaconitine exhibits higher bioavailability in female rats, as compared with male rats.

High-strength, transparent and superhydrophobic nanocellulose/nanochitin membranes fabricated via crosslinking of nanofibers and coating F-SiO2 suspensions.

In this study, nanocellulose/nanochitin membranes were prepared by suction filtrating 2,2,6,6-tetramethylpiperidine-1-oxyl-oxidized cellulose nanofiber (TOCNF)/partially deacetylated α-chitin nanofiber (α-DECHN) mixed suspensions. The result shows that, with a 1:1 ratio of nanocellulose to nanochitin, the tensile strength of the obtained composite membrane reaches 115.7 MPa and its light transmittance is 77.6 %. Heptadecafluoro-1,1,2,2-tetrahydrodecyl dimethylchlorosilane (HFTD) modified nano SiO2 (F-SiO2), was utilized to construct rough micro/nanostructures on the surfaces of the composite membranes by screen printing, forming high-strength, transparent and superhydrophobic nanocellulose/nanochitin membranes. Atomic force microscope (AFM) images reveal that nanocellulose and nanochitin, with the width between 5 nm and 20 nm and the length between 400 nm and 1.1 µm, are crosslinked with each other. The superhydrophobic nanocellulose/nanochitin composite membranes functionalized with a 2.0 wt% F-SiO2 suspension has a few clusters on its surface. The contact angle of this membrane is 150.1°, and its light transmittance is 70.4 %.

Helicid Reverses Lipopolysaccharide-Induced Inflammation and Promotes GDNF Levels in C6 Glioma Cells through Modulation of Prepronociceptin.

Helicid suppresses inflammatory factors and protects nerve cells in the hippocampus of rats with depression, but the mechanisms underlying its protective effects are unclear at present. In this investigation, we conducted gene silencing, Helicid intervention and rescue experiments to explore the protective actions of PNOC, the prepronociceptin gene known to regulate inflammatory processes, and Helicid on a C6 cell model of inflammation induced by LPS. Collective data from Western blots, ELISA, immunofluorescence and flow cytometry experiments showed that PNOC silencing or administration of Helicid led to reduced inflammatory factor levels, oxidative stress and expression of glial fibrillary acidic protein (GFAP), along with increased glial cell lines-derived neurotrophic factor (GDNF) expression. Furthermore, expression of p-Akt in the Akt signaling pathway was increased. Interestingly, overexpression of PNOC in the Helicid treatment group partially reversed the Helicid-induced changes in the above biochemical indexes. Our collective results provide strong evidence of Helicid-mediated regulation of the Akt signaling pathway through PNOC to improve cell inflammation and oxidative stress.

Altered attention networks in patients with thyroid dysfunction: A neuropsychological study.

Patients with thyroid dysfunction (31 hypothyroid, 32 subclinical hypothyroidism, 34 hyperthyroid, and 30 subclinical hyperthyroidism) and 37 euthyroid control subjects were recruited and performed the attention network test (ANT), which can simultaneously examine the alertness, orientation and execution control of the participants. Patients with hypothyroidism had abnormalities in the alerting network, and those with hyperthyroidism had impairments of the alerting and executive control networks. No attention networks deficit existed in patients with subclinical hyperthyroidism and subclinical hypothyroidism. The anxiety and depression scores of patients with thyroid dysfunction were significantly higher than those of the healthy control group. Covariance analysis demonstrated that interactions between group and Hamilton Anxiety Scale scores, group and HAMD score were not significant, but there was a significant main effect for group when analyzing the difference in values of the alerting network between groups. Further, the efficiency of the executive control network was negatively correlated with the T4 level in the hypothyroidism group, and positively correlated with the T4 level in the hyperthyroidism group. T4 or T3 level and efficiencies of the executive control network had a significant quadratic U-shaped relationship in all participants. In summary, the patients with four kinds of thyroid dysfunction exhibited different characteristics of ANT performance. Patients with thyroid dysfunction had various degrees of anxiety and depression disorders, but anxiety and depression disorders had no effect on the differences in the executive control network between the groups.

MST4 modulates the neuro-inflammatory response by regulating IκBα signaling pathway and affects the early outcome of experimental ischemic stroke in mice.

MST4 limits peripheral, macrophage-dependent inflammatory responses through direct phosphorylation of the adaptor TRAF6; though its role in neuro-inflammation is unclear. We investigated microglia expression of MST4 and whether is attenuates neuro-inflammatory response after cerebral ischemia-reperfusion injury in mice. Adult male C57BL6 mice were subjected to a 90-minute middle cerebral artery occlusion (MCAO) followed by a 72 -h reperfusing. The results showed that MST4 was involved in the pathological process after cerebral ischemia-reperfusion and was expressed in microglia. MST4-Adeno Associated Virus attenuated brain damage after MCAO and reduced expression of p-IκBα, p-ERK and p-JNK, while MST4 shRNA aggravated brain damage after MCAO and increased expression of p-IκBα, p-ERK and p-JNK. Our results show that MST4 inhibits neuro-inflammatory response in cerebral ischemia-reperfusion injury, improves neurological deficits, and reduces cerebral infarction volume in mice. Strategies to enhance MST4 in response to ischemic stroke may be a potential therapeutic strategy.

Efficacy and Safety of Intravenous Thrombolysis in Patients with Unknown Onset Stroke: A Meta-Analysis.

OBJECTIVES: Unknown onset stroke (UOS) is usually excluded from intravenous thrombolysis concerning the unclear symptom onset time. Attempts have been done to use thrombolytic therapy in these patients. The current meta-analysis was done to examine the efficacy and safety of intravenous thrombolysis in UOS. METHODS: PubMed, Web of Science, and Cochrane Library were searched for studies comparing thrombolysis with conservative therapy among UOSs. Data of good outcome (mRS, 0-2), mortality, and intracerebral hemorrhage (ICH) and symptomatic ICH (sICH) were extracted and analyzed using the Revman 5.2 software. RESULTS: In total, 8 studies with 1271 subjects (542 with thrombolysis and 729 with conservative therapy) were included in this meta-analysis. The data showed that patients receiving thrombolysis had a higher incidence of 90-day good outcome (P = 0.0005) than conservative therapy. The comparison of discharge (P = 0.89) and 90-day mortality (P = 0.10) in both groups did not find any significances. The incidences of ICH (P = 0.42) and sICH (P = 0.06) were relatively comparable between the two therapies. CONCLUSIONS: Intravenous thrombolysis is a better choice for UOS patients for its efficacy and safety. In addition, pretreatment imaging assessment is beneficial for improving the efficacy of thrombolytic therapy. However, it needs more supporting evidences for clinical use in the future.

Helicid Ameliorates Learning and Cognitive Ability and Activities cAMP/PKA/CREB Signaling in Chronic Unpredictable Mild Stress Rats.

Helicid (4-formylphenyl-O-ß-D-allopyranoside), an active component found in seeds from the Chinese herb Helicia nilagirica, has been reported to exert sedative, analgesic, hypnotic and antidepressant effects. The present study was designed to evaluate the antidepressant, learning and cognitive improvement effects of helicid in a chronic unpredictable mild stress (CUMS) model of depression in rats and to explore cAMP/protein kinase A (PKA)/cAMP response element-binding (CREB) signaling pathway. Sprague-Dawley rats were randomly assigned to six groups (n = 10): control; CUMS; CUMS + fluoxetine (5 mg/kg) and CUMS + helicid at 8, 16 and 32 mg/kg. All rats were subjected to 12 weeks of CUMS protocols and drug administration during the last 6 weeks of CUMS. Our results showed that helicid, at a dose of 32 mg/kg, significantly reversed decreases in body weight and sucrose consumption, increased the distance and number of crossings in the open-field test (OFT), reduced immobility times in the forced swimming test (FST) and improved spatial memory in the Morris water maze (MWM); all of these effects had been induced by CUMS paradigm. Immunohistochemistry showed that administration of helicid could promoted the proliferation of neurons in the hippocampal CA1 and dentate gyrus (DG) regions. CUMS rats treated with helicid had dramatically decreased protein levels of serotonin transporters (SERTs). In addition, CUMS resulted in a significant reduction in the expression of cAMP, PKA C-α and p-CREB, each of which were partially attenuated by helicid administration. These results indicated that helicid could improve depressive behaviors, learning and cognitive deficits and increase hippocampal neurogenesis, which may be mediated by the regulation of SERTs, activation of the cAMP/PKA/CREB signaling pathway and upregulation of p-CREB levels in hippocampal.