Ginsenoside Rd reduces cell proliferation of non-small cell lung cancer cells by p53-mitochondrial apoptotic pathway.

Ginsenoside Rd is a tetracyclic triterpenoid derivative, widely existing in Panax ginseng, Panax notoginseng and other traditional Chinese medicines. Many studies have proved that ginsenoside Rd have a variety of significant biological activities on certain types of cancer. However, the mechanism of ginsenoside Rd remains unclear in lung cancer. The findings of this study reveal that GS-Rd inhibits the proliferation of NSCLC cells, induces apoptosis, and suppresses migration and invasion. The results showed Ginsenoside Rd inhibited the cell proliferation (∼99.52 %) by S phase arrest in cell cycle and promoted the apoptosis (∼54.85 %) of NSCLC cells. It also inhibited the migration and invasion of cells (p < 0.001). The expression levels of related mitochondrial apoptosis proteins (Bax/Bcl-2/Cytochrome C) and matrix metalloproteinases (MMP-2/-9) were significantly changed. The results showed that ginsenoside Rd inhibited the proliferation of tumor cells by activating p53/bax-mediated mitochondrial apoptosis and the expression of key enzymes for cell apoptosis caspase-3/cleaved-caspase-3 were significantly increased. This research contributes to a better understanding of the anti-tumor effects and molecular mechanisms of GS-Rd, paving the way for its potential development and clinical application in NSCLC therapy.

Review on active components and mechanism of natural product polysaccharides against gastric carcinoma.

One of the malignant tumors with a high occurrence rate worldwide is gastric carcinoma, which is an epithelial malignant tumor emerging from the stomach. Natural product polysaccharides are a kind of natural macromolecular polymers, which have the functions of regulating immunity, anti-oxidation, anti-fatigue, hypoglycemia, etc. Natural polysaccharides have remarkable effectiveness in preventing the onset, according to studies, and development of gastric cancer at both cellular and animal levels. This paper summarizes the inhibitory mechanisms and therapeutic significance of plant polysaccharides, fungi polysaccharides, and algal polysaccharides in natural product polysaccharides on the occurrence and development of gastric cancer in recent years, providing a theoretical basis for the research, development, and medicinal value of polysaccharides.

Platelet count and clinical outcomes among ischemic stroke patients with endovascular thrombectomy in DIRECT-MT.

OBJECTIVES: The prognostic role of baseline platelet count (PLT) in acute ischemic stroke patients with large vessel occlusion undergoing endovascular thrombectomy is unclear. Whether PLT modifies alteplase treatment effect on clinical outcome in those patients is also uncertain. METHODS: We derived data from a multicenter randomized clinical trial (DIRECT-MT) comparing intravenous alteplase before endovascular treatment vs. endovascular treatment only. The 654 patients with available PLT data were included. Primary outcome was the ordinal modified Rankin Scale (mRS) score evaluated at 90 days. We also assessed various secondary and safety outcomes. RESULTS: After adjusting for confounding factors, patients in the top tertile of PLT had a significantly lower risk of a worse shift in the distribution of mRS score (Odds Ratio: 0.671, 95% Confidence Interval: 0.473-0.953, p for trend=0.025), major disability and death (Odds Ratio: 0.617, 95% Confidence Interval: 0.393-0.97, p for trend=0.037) as well as death (Odds Ratio: 0.544, 95% Confidence Interval: 0.313-0.947, p for trend=0.031), respectively, compared with the bottom one. Among patients in the bottom tertile of PLT, combination therapy was associated with a better imaging outcome of eTICI score of 2b, 2c or 3 on final angiogram (Odds Ratio: 3.23, 95% Confidence Interval: 1.49-7.002) with a marginally significant interaction effect. CONCLUSIONS: Participants with higher baseline PLT had a decreased risk of poor functional outcomes. Low baseline PLT modified alteplase treatment effect on the eTICI score on final angiogram. Combination therapy was beneficial for patients with low baseline PLT to have a better reperfusion status.

Primary intracranial extraskeletal myxoid chondrosarcoma: A case report and review of literature.

BACKGROUND: Primary intracranial extraskeletal myxoid chondrosarcoma (EMC) is an extremely rare low- to intermediate-grade malignant soft tissue sarcoma, and only 15 cases have been reported in the literature. Due to its rarity, clinical data and research on this tumor type are extremely limited, the pathogenesis and histological origin are still unclear, and the diagnostic and standard clinical treatment strategies for intracranial EMC remain controversial and undefined. CASE SUMMARY: We reported a case of a 52-year-old male who was admitted to the hospital with headache and dizziness for 1 mo, and his health status deteriorated during the last week. CT of the head showed a well-defined low-density lesion situated in the left cavernous sinus. Brain magnetic resonance imaging (MRI) showed a 3.4 cm × 3.0 cm sized, well-defined, round-shaped and heterogeneously enhanced lesion located in the left cavernous sinus. The entire lesion was removed via supratentorial craniotomy and microsurgery. Postoperative pathological diagnosis indicated primary intracranial EMC. Subsequently, the patient underwent 45 Gy/15 F stereotactic radiotherapy after discharge. At present, it is 12 mo after surgery, with regular postoperative follow-up and regular MRI examinations, that there are no clinical symptoms and radiographic evidence indicating the recurrence of the tumor, and the patient has returned to normal life. CONCLUSION: Currently, the most beneficial treatment for primary intracranial EMC is gross total resection combined with postoperative radiotherapy. Long-term follow-up is also necessary for patients.

Structural characterisation and antitumor activity against non-small cell lung cancer of polysaccharides from Sanghuangporus vaninii.

The medicinal fungus Sanghuangporus vaninii can be cultivated in large scale and has outstanding antitumour activity. In this study, water-soluble S. vaninii polysaccharides (SVPs) were extracted from fruiting bodies. Four polysaccharide sub-fractions (SVP-W, SVP-1, SVP-2 and SVP-3) were isolated, with molecular weights from 90.50 kDa to 261.70 kDa, and all inhibited the proliferation of non-small cell lung cancer cell lines A549, 95-D and NCI-H460, especially the acidic SVP-1. SVP-1 affected cell morphology and colony formation in NCI-H460 cells. It also promoted cell apoptosis following nuclear fluorescence staining and flow cytometry. Methylation and nuclear magnetic resonance analyses revealed that SVP-1 is a heteroglycan with the main chain →4)-ß-D-Glcp-(1 â†’ 6)-ß-D-Glcp-(1 â†’ 6)-α-D-Galp-(1 â†’ 6)-ß-D-Glcp-(1→, and the branched chain α-D-Manp-(1 â†’ 2)-α-D-Manp-(1 â†’ 3)-ß-D-Glcp-(1 â†’ 3,6)-ß-D-Glcp-(1→. The findings indicate that this natural acidic polysaccharide has potential for non-small cell lung cancer therapy.

Primary Intracranial Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Mimicking Meningioma: A Case Report and Literature Review.

Background: Primary intracranial Ewing sarcoma (ES)/peripheral primitive neuroectodermal tumors (pPNETs) are extremely rare malignancies, which arise in children and adolescents, with only 9 cases reported in patients over 30 years of age. Due to its rarity, MRI features and treatment strategies for primary intracranial ES/pPNETs remain unclear. The purpose of this study was to explore the clinical features, imaging findings, pathological characteristics, different diagnoses, treatment, and prognosis of cerebellar liponeurocytoma in adults. Case Description: A 55-year-old female was admitted to the hospital with memory decline over 1 month, which aggravated in the last 2 weeks. MRI showed a 4.3 × 6.5 × 3.5 cm heterogeneous large mass in the left frontal lobe with mild peritumoral edema. The mass was successfully removed under neuronavigation and electrophysiological monitoring. The entire mass was removed, and postoperative pathology indicated an ES pPNET diagnosis, with an EWSR1 gene rearrangement. Subsequently, the patient underwent disciplinary radiotherapy. Conclusion: The diagnosis of primary intracranial ES/pPNETs depends on the comprehensive consideration of histological examination, immunohistochemical analysis, and genetic detection. Gross tumor resection combined with radiotherapy and chemotherapy might be the most beneficial treatment.

Dexmedetomidine Added to Sufentanil Patient-Controlled Intravenous Analgesia Relieves the Postoperative Pain after Cesarean Delivery: A Prospective Randomized Controlled Multicenter Study.

This study evaluated the efficacy and safety of dexmedetomidine in intravenous patient-controlled analgesia (PCA) after cesarean delivery. This multicenter study enrolled 208 subjects who were scheduled for selective cesarean delivery from 9 research centers. Patients received 0.5 ug/kg dexmedetomidine (study group) or normal saline (control group) after delivery and an intravenous PCA pump after surgery (100 µg sufentanil +300 µg dexmedetomidine for the study group, 100 µg sufentanil for the control group, background infusion: 1 ml/h, bolus dose: 2 ml and lock time: 8 min). The sufentanil consumption, pain scores, rescue analgesia, sedation scores, analgesic satisfaction, the incidence of postoperative nausea and vomiting (PONV) and the first passage of flatus were recorded within 24 h after surgery. The sufentanil consumption in the study group was significantly lower than that in the control group (p = 0.004). Compared with the control group, the study group had lower pain scores (p < 0.01), higher analgesic satisfaction degree [p < 0.001, odd ratio 4.28 and 95% CI (2.46, 7.46)], less requirement of rescue analgesia (p = 0.003), lower incidence of PONV (p = 0.005 and p < 0.001, respectively), and shorter time to first passage of flatus (p = 0.007). Dexmedetomidine added to sufentanil intravenous PCA significantly enhanced the analgesic effects, improved analgesic satisfaction, and had the potential benefits of reducing PONV and the recovery of intestinal functions after cesarean section.

FOXG1 Expression Is Elevated in Glioma and Inhibits Glioma Cell Apoptosis.

FOXG1, a member of forkhead family transcriptional factor, is involved in telencephalon development. Recent studies showed FOXG1 was important for a variety of cellular events in cancer cells. In respect to glioma, FOXG1 has been shown to regulate cell proliferation and cell cycles. However, its impacts on other cellular events were not well studied. Here, we found FOXG1 had high expression in clinical glioma tissues, and its expression positively correlated with glioma malignancy. Moreover, we found FOXG1 played roles in glioma cell apoptosis. The expressions of caspase family members were significantly altered in response to change of FOXG1 expression, indicating a direct regulation of FOXG1 on caspase family members. These data strongly suggest FOXG1 is negative regulator of glioma cell apoptosis.

Extraventricular Neurocytoma in the Left Frontal Lobe: A Case Report and Literature Review.

BACKGROUND: Neurocytoma is a rare brain neoplasm of neuroepithelial origin that occurs predominantly in the ventricular system adjacent to the interventricular foramen and septum pellucidum. However, extraventricular neurocytoma is an extremely rare entity, with poor clinical, radiologic, and histopathological characterization. Here we report a case of an extraventricular parafalcine neurocytoma in the left frontal lobe. We also examine previously reported cases of extraventricular neurocytoma in an attempt to provide an up-to-date summary of the condition. METHODS: A literature search was performed using PubMed with specific key terms, inclusion criteria, and exclusion criteria. Selected case studies and case series were then compared, and statistical analyses were performed where appropriate. We report a 59-year-old woman presenting with weakness in her right leg and urinary incontinence. Physical examination revealed muscle strength of grade 3/5 in the right lower extremity. Brain magnetic resonance imaging showed a parafalcine mass in the left frontal lobe, with perilesional edema; the cerebral falx and lateral ventricle were shifted due to the compression. Gross total resection was performed. RESULTS: Histopathological examination revealed a neurocytoma. Immunohistochemical staining showed diffuse positivity for synaptophysin. MIB-1 staining for Ki-67 antibody showed a labeling index of 20%. No adjuvant radiation or chemotherapy was administered. Brain computed tomography performed at a 3-month follow-up showed no signs of recurrence. CONCLUSION: Extraventricular neurocytoma occurring in the brain parenchyma is a very rare central nervous system tumor. Its clinical and radiologic manifestations are nonspecific. The diagnosis depends on histopathological and immunohistochemical examination. Surgical resection should be the first-choice treatment.

Age Does Not Affect Metoprolol's Effect on Perioperative Outcomes (From the POISE Database).

BACKGROUND: Perioperative ß-blockade reduces the incidence of myocardial infarction but increases that of death, stroke, and hypotension. The elderly may experience few benefits but more harms associated with ß-blockade due to a normal effect of aging, that of a reduced resting heart rate. The tested hypothesis was that the effect of perioperative ß-blockade is more significant with increasing age. METHODS: To determine whether the effect of perioperative ß-blockade on the primary composite event, clinically significant hypotension, myocardial infarction, stroke, and death varies with age, we interrogated data from the perioperative ischemia evaluation (POISE) study. The POISE study randomly assigned 8351 patients, aged ≥45 years, in 23 countries, undergoing major noncardiac surgery to either 200 mg metoprolol CR daily or placebo for 30 days. Odds ratios or hazard ratios for time to events, when available, for each of the adverse effects were measured according to decile of age, and interaction term between age and treatment was calculated. No adjustment was made for multiple outcomes. RESULTS: Age was associated with higher incidences of the major outcomes of clinically significant hypotension, myocardial infarction, and death. Age was associated with a minimal reduction in resting heart rate from 84.2 (standard error, 0.63; ages 45-54 years) to 80.9 (standard error, 0.70; ages >85 years; P < .0001). We found no evidence of any interaction between age and study group regarding any of the major outcomes, although the limited sample size does not exclude any but large interactions. CONCLUSIONS: The effect of perioperative ß-blockade on the major outcomes studied did not vary with age. Resting heart rate decreases slightly with age. Our data do not support a recommendation for the use of perioperative ß-blockade in any age subgroup to achieve benefits but avoid harms. Therefore, current recommendations against the use of ß-blockers in high-risk patients undergoing noncardiac surgery apply across all age groups.

The effects of halogen elements on the opening of an icosahedral B12 framework.

The fully halogenated or hydrogenated B12X122- (X = H, F, Cl, Br and I) clusters are confirmed to be icosahedral. On the other hand, the bare B12 cluster is shown to have a planar structure. A previous study showed that a transformation from an icosahedron to a plane happens when 5 to 7 iodine atoms are remained [P. Farràs et al., Chem. - Eur. J. 18, 13208-13212 (2012)]. Later, the transition was confirmed to be seven iodine atoms based on an infrared spectroscopy study [M. R. Fagiania et al., Chem. Phys. Lett. 625, 48-52 (2015)]. In this study, we investigated the effects of different halogen atoms on the opening of the B12 icosahedral cage by means of density functional theory calculations. We found that the halogen elements do not have significant effects on the geometries of the clusters. The computed infrared (IR) spectra show similar representative peaks for all halogen doped clusters. Interestingly, we found a blue-shift in the IR spectra with the increase in the mass of the halogen atoms. Further, we compared the Gibbs free energies at different temperatures for different halogen atoms. The results show that the Gibbs free energy differences between open and close structures of B12X7- become larger when heavier halogen atoms are presented. This interesting finding was subsequently investigated by the energy decomposition analysis.

Netrin-1 promotes glioma growth by activating NF-κB via UNC5A.

Gliomas, a common type of brain tumor, are characterized by aggressive infiltration, making it difficultly to cure by surgery. Netrin-1, an extracellular guidance cue critical for neuronal axon path-finding, has been reported to play an important role in cell invasion and migration in several types of cancers. However, the role of netrin-1 in glioma remains largely unknown. Here, we provide evidence suggested that Netrin-1 has a critical role in glioma growth. We found that netrin-1 was significantly increased in glioma samples and positively correlated with cell proliferation, tumor grade and malignancy. Netrin-1 knockdown reduced cell proliferation and attenuated tumor growth in a xenograft mouse model. Further studies found that netrin-1 induced NF-κB p65ser536 phosphorylation and c-Myc expression in vitro and in vivo. Interestingly, activation of NF-κB by netrin-1 was dependent on UNC5A receptor, because suppression of UNC5A significantly inhibited NF-κB p65ser536 phosphorylation, c-Myc up-regulation and reduced cell proliferation. Taken together, these results suggested netrin-1 promotes glioma cell proliferation by activating NF-κB signaling via UNC5A, netrin-1 may be a potential therapeutic target for the treatment of glioma.

Telomere targeting with a novel G-quadruplex-interactive ligand BRACO-19 induces T-loop disassembly and telomerase displacement in human glioblastoma cells.

Interference with telomerase and telomere maintenance is emerging as an attractive target for anticancer therapies. Ligand-induced stabilization of G-quadruplex formation by the telomeric DNA 3'-overhang inhibits telomerase from catalyzing telomeric DNA synthesis and from capping telomeric ends, making these ligands good candidates for chemotherapeutic purposes. BRACO-19 is one of the most effective and specific ligand for telomeric G4. It is shown here that BRACO-19 suppresses proliferation and reduces telomerase activity in human glioblastoma cells, paralleled by the displacement of telomerase from nuclear to cytoplasm. Meanwhile, BRACO-19 triggers extensive DNA damage response at telomere, which may result from uncapping and disassembly of telomeric T-loop structure, characterized by the formation of anaphase bridge and telomere fusion, as well as the release of telomere-binding protein from telomere. The resulting dysfunctional telomere ultimately provokes p53 and p21-mediated cell cycle arrest, apoptosis and senescence. Notably, normal primary astrocytes do not respond to the treatment of BRACO-19, suggesting the agent's good selectivity for cancer cells. These results reinforce the notion that G-quadruplex binding compounds can act as broad inhibitors of telomere-related processes and have potential as selective antineoplastic drugs for various tumors including malignant gliomas.

Incidence of postoperative residual neuromuscular blockade after general anesthesia: a prospective, multicenter, anesthetist-blind, observational study.

OBJECTIVE: Evidences demonstrate that postoperative residual neuromuscular blockade (rNMB) is a primary and frequent anesthetic risk factor for postoperative complications. This study was designed to mitigate the paucity of data regarding the occurrence and degree of rNMB in a real-life setting. METHODS: This prospective, multicenter, anesthetist-blind, observational study enrolled 1571 Chinese adults undergoing elective open or laparoscopic abdominal surgery lasting ≤4 hours from 32 hospitals across China. The patients received anesthesia in accordance with routine practice at the study site. Neuromuscular blockade (NMB) was monitored using acceleromyography, with rNMB defined as a train-of-four (TOF) ratio <0.9. RESULTS: The patients' mean age was 46 years and 71% were female. The procedures included laparoscopic (67%), open abdominal (31%), and laparoscopic to open abdominal (2%). NMB was reversed with neostigmine in 78% of patients. The overall incidence of rNMB at extubation was 57.8%, and the proportions of participant with TOF ratios <0.6, 0.6-0.7, 0.7-0.8, 0.8-0.9 were 22.9%, 6.9%, 11.1% and 16.9%, respectively, immediately prior to endotracheal extubation. Age <45 years (OR = 0.630, 95% CI = 0.496-0.801, p = 0.002), use of one neuromuscular blocking agent (NMBA) (OR = 0.387, 95% CI = 0.243-0.618, p < 0.0001), time from neostigmine administration to endotracheal extubation ≥10 min (OR = 0.513, 95% CI = 0.400-0.658, p < 0.0001) and time from last NMBA administration to endotracheal extubation ≥60 min (OR = 0.902, 95% CI = 0.801-0.989, p = 0411) were correlated with non-rNMB at the time of extubation. CONCLUSIONS: This observational study demonstrated that the overall incidence of rNMB at the time of endotracheal extubation was high in Chinese patients undergoing abdominal procedures, which necessitates appropriate management in current real-life practice. CLINICAL TRIAL REGISTRY NUMBER: NCT01871064.

Bipolar membrane electrodialysis for generation of hydrochloric acid and ammonia from simulated ammonium chloride wastewater.

Simulated ammonium chloride wastewater was treated by a lab-scale bipolar membrane electrodialysis for the generation of HCl and NH3·H2O and desalination. The influence of initial concentration of NH4Cl, current density, salt solution volume, initial concentration of acid and base and membrane stack structure on the yields of HCl and NH3·H2O was investigated. The current efficiency and energy consumption were also examined under different conditions. The results showed that, at the current density of 48 mA/cm(2), the highest concentration of HCl and NH3·H2O with initial concentration of 110 g/L NH4Cl was 57.67 g/L and 45.85 g/L, respectively. Higher initial concentration of NH4Cl was favor to reduce unit energy consumption and increase current efficiency of the BMED system. The membrane stack voltage of BMED increased quickly under constant current when the concentration of NH4Cl contained in the solution of salt compartment was depleted below the "inflection point concentration" about 8000 mg/L. It means that the concentration of NH4Cl below 8000 mg/L was no longer suitable for BMED because of higher energy consumption. The HCl and NH3·H2O concentration increased more quickly following the increase of current density. When increasing the volume of NH4Cl, the concentration of HCl and NH3·H2O also increased. The high initial concentration of acid and base could improve the final concentration of them, while the growth rate was decreased. Compared with the BMED system with three compartments, the growth rate of HCl concentration with the two compartments was higher and its unit energy consumption was lower. It meant that the performance of the BMED system could be improved by optimizing operation conditions. The application feasibility of the generation of HCl and NH3·H2O and desalination of ammonium chloride wastewater by BMED was proved.

Up-Regulation of Corticocerebral NKD2 in Lipopolysaccharide-Induced Neuroinflammation.

Naked2 (NKD2), one member of Naked family, has been shown to negatively regulate Wnt/ß-catenin signaling pathway. It has been recognized that NKD2 plays a vital role in cell homeostasis and prevention of tumorigenesis. However, NKD2 expression and its functional role in the brain in neuroinflammatory processes remain unclear. In our study, we investigated NKD2 distribution and role in lipopolysaccharide (LPS)-induced neuroinflammation rat model. The data indicated that NKD2 was up-regulated in LPS-injected brain, and the cellular localization of NKD2 was predominantly in cerebral cortical neurons. Furthermore, we treated primary neurons with conditioned media (CM) collected from LPS-stimulated mixed glial cultures (MGC). We detected that the up-regulation of NKD2 might be associated with the subsequent apoptosis in neurons. We also found knockdown NKD2 partially depressed the increase of cleaved caspase-3 and increased the reduction of ß-catenin stimulated by MGC-CM. Taken together, these results suggested that NKD2 might be involved in neuronal apoptosis via the Wnt/ß-catenin pathway during neuroinflammation in CNS. Our findings might provide a new therapeutic target for the prevention of neuroinflammation-involved neurological disorders.

Up-Regulation of CCT8 Related to Neuronal Apoptosis after Traumatic Brain Injury in Adult Rats.

Traumatic brain injury (TBI) initiates a series of neurochemical and signaling changes that could eventually lead to neuronal apoptosis. Recent studies indicated that mature neurons cell cycle re-enter played a crucial role in neuronal apoptosis. In this study, we identified that the chaperonin containing TCP-1, subunit 8 (CCT8), as a member of class II chaperonins, was significantly upregulated following TBI. Moreover, double immunofluorescence staining revealed that CCT8 was co-expressed with neuronal nuclei (NeuN). Besides, co-localization of CCT8/active caspase 3 was detected in NeuN. We also examined the expression profiles of active caspase 3 whose changes were correlated with the expression of CCT8. All our findings suggested that CCT8 might be involved in the pathophysiology of brain after TBI.

Salvianolic Acid B Ameliorates Lipopolysaccharide-Induced Albumin Leakage from Rat Mesenteric Venules through Src-Regulated Transcelluar Pathway and Paracellular Pathway.

Lipopolysaccharide (LPS) causes microvascular barrier disruption, leading to albumin leakage from microvessels resulting in a range of disastrous sequels. Salvianolic acid B (SalB) is a major water-soluble component derived from Salvia miltiorrhiza. Previous studies showed its potential to attenuate microvascular barrier dysfunction, but the underlying mechanism is not fully understood. The present study was intended to investigate the impact of SalB on endothelial cell barrier in vivo in rat mesenteric venules as well as in vitro in human umbilical vein endothelial cells (HUVECs), aiming at disclosing the mechanism thereof, particularly the role of Src in its action. Male Wistar rats were challenged by infusion of LPS (2 mg/kg/h) through left femoral vein for 90 min. SalB (5 mg/kg/h) was administrated either simultaneously with LPS or 30 min after LPS infusion through the left jugular vein. Vesicles in venular walls were observed by electron microscopy. HUVECs were incubated with LPS with or without SalB. The expression of Zonula occluden-1 (ZO-1), VE-cadherin, caveolin-1 and Src in HUVECs was assessed by Western blot and confocal microscopy, binding of SalB to Src was measured using Surface Plasmon Resonance and BioLayer Interferometry. Treatment with SalB inhibited albumin leakage from rat mesenteric venules and inhibited the increase of vesicle number in venular endothelial cells induced by LPS. In addition, SalB inhibited the degradation of ZO-1, the phosphorylation and redistribution of VE-cadherin, the expression and phosphorylation of caveolin-1, and phosphoirylation of Src in HUVECs exposed to LPS. Furthermore, SalB was found able to bind to Src. This study demonstrates that protection of SalB against microvascular barrier disruption is a process involving both para- and trans-endothelial cell pathway, and highly suggests Src as the key enzyme for SalB to work.

Thoracic epidural anesthesia improves outcomes in patients undergoing cardiac surgery: meta-analysis of randomized controlled trials.

To assess the efficacy of thoracic epidural anesthesia (TEA) with or without general anesthesia (GA) versus GA in patients who underwent cardiac surgery, PubMed, Embase, the Cochrane online database, and Web of Science were searched with the limit of randomized controlled trials (RCTs) relevant to 'thoracic epidural anesthesia' and 'cardiac surgery'. Studies were identified and data were extracted by two reviewers independently. The quality of included studies was also assessed according to the Cochrane handbook. Outcomes of mortality, cardiac and respiratory functions, and treatment-associated complications were pooled and analyzed. The comprehensive search yielded 2,230 citations, and 25 of them enrolling 3,062 participants were included according to the inclusion criteria. Compared with GA alone, patients received TEA and GA showed reduced risks of death, myocardial infarction, and stroke, though there were no significant differences (P > 0.05). With regard to treatment-related complications, the pooled results for respiratory complications (risk ratio (RR), 0.69; 95% CI: 0.51, 0.91, P < 0.05), supraventricular arrhythmias (RR, 0.61; 95% CI: 0.42, 0.87, P < 0.05), and pain (mean difference (MD), -1.27; 95% CI: -2.20, -0.35, P < 0.05) were 0.69, 0.61, and -1.27, respectively. TEA was also associated with significant reduction of stays in intensive care unit (MD, -2.36; 95% CI: -4.20, -0.52, P < 0.05) and hospital (MD, -1.51; 95% CI: -3.03, 0.02, P > 0.05) and time to tracheal extubation (MD, -2.06; 95% CI:-2.68, -1.45, P < 0.05). TEA could reduce the risk of complications such as supraventricular arrhythmias, stays in hospital or intensive care unit, and time to tracheal extubation in patients who experienced cardiac surgery.

The role of Homer1b/c in neuronal apoptosis following LPS-induced neuroinflammation.

Homer, also designated Vesl, is one member of the newly found postsynaptic density scaffold proteins, playing a vital role in maintaining synaptic integrity, regulating intracellular calcium mobilization, and being critical for the regulation of cellular apoptosis. However, its function in the inflamed central nervous system (CNS) is not fully elucidated. Here, we investigated the role of Homer1b/c, a long form of Homer1, in lipopolysaccharide (LPS) induced neuroinflammation in CNS. Western blot analysis indicated that LPS administration significantly increased the expression of Homer1b/c in rat brain. Moreover, double immunofluorescent staining suggested Homer1b/c was mainly distributed in the cytoplasm of neurons and had a close association with cleaved caspase-3 level in neurons in rat brain after LPS injection. In vitro studies indicated that up-regulation of Homer1b/c might be related to the subsequent apoptosis in neurons treated by conditioned media (CM), collected from LPS-stimulated mixed glial cultures (MGC). We also found down-regulation of Homer1b/c partly blocked the increase of cleaved caspase-3 and the proportion of Bax/Bcl-2 in neurons induced by MGC-CM. Taken together, these findings suggested that Homer1b/c might promote neuronal apoptosis via the Bax/Bcl-2 dependent pathway during neuroinflammation in CNS, and inhibiting Homer1b/c expression might provide a novel neuroprotective strategy against the inflammation-related neuronal apoptosis.