Comparison of O-RADS, GI-RADS, and ADNEX for Diagnosis of Adnexal Masses: An External Validation Study Conducted by Junior Sonologists.

OBJECTIVE: To externally validate the Ovarian-adnexal Reporting and Data System (O-RADS) and evaluate its performance in differentiating benign from malignant adnexal masses (AMs) compared with the Gynecologic Imaging Reporting and Data System (GI-RADS) and Assessment of Different NEoplasias in the adneXa (ADNEX). METHODS: A retrospective analysis was performed on 734 cases from the Second Affiliated Hospital of Fujian Medical University. All patients underwent transvaginal or transabdominal ultrasound examination. Pathological diagnoses were obtained for all the included AMs. O-RADS, GI-RADS, and ADNEX were used to evaluate AMs by two sonologists, and the diagnostic efficacy of the three systems was analyzed and compared using pathology as the gold standard. We used the kappa index to evaluate the inter-reviewer agreement (IRA). RESULTS: A total of 734 AMs, including 564 benign masses, 69 borderline masses, and 101 malignant masses were included in this study. O-RADS (0.88) and GI-RADS (0.90) had lower sensitivity than ADNEX (0.95) (P < .05), and the PPV of O-RADS (0.98) was higher than that of ADNEX (0.96) (P < .05). These three systems showed good IRA. CONCLUSION: O-RADS, GI-RADS, and ADNEX showed little difference in diagnostic performance among resident sonologists. These three systems have their own characteristics and can be selected according to the type of center, access to patients' clinical data, or personal comfort.

eNOS-Nitric Oxide System Contributes to a Novel Antiatherogenic Effect of Leonurine via Inflammation Inhibition and Plaque Stabilization.

Leonurine (LEO) is a bioactive small molecular compound that has protective effects on the cardiovascular system and prevents the early progression of atherosclerosis; however, it is not clear whether LEO is effective for plaque stability. A novel mouse atherosclerosis model involving tandem stenosis (TS) of the right carotid artery combined with western diet (WD) feeding was used. Apolipoprotein E gene-deficient mice were fed with a WD and received LEO administration daily for 13 weeks. TS was introduced 6 weeks after the onset of experiments. We found that LEO enhanced plaque stability by increasing fibrous cap thickness and collagen content while decreasing the population of CD68-positive cells. Enhanced plaque stability by LEO was associated with the nitric oxide synthase (NOS)-nitric oxide (NO) system. LEO restored the balance between endothelial NOS(E)- and inducible NOS(iNOS)-derived NO production; suppressed the NF-κB signaling pathway; reduced the level of the inflammatory infiltration in plaque, including cytokine interleukin 6; and downregulated the expression of adhesion molecules. These findings support the distinct role of LEO in plaque stabilization. In vitro studies with oxidized low-density lipoprotein-challenged human umbilical vein endothelial cells revealed that LEO balanced NO production and inhibited NF-κB/P65 nuclear translocation, thus mitigating inflammation. In conclusion, the restored balance of the NOS-NO system and mitigated inflammation contribute to the plaque-stabilizing effect of LEO. SIGNIFICANCE STATEMENT: LEO restored the balance between endothelial NOS and inducible NOS in NO production and inhibited excessive inflammation in atherosclerotic "unstable" and rupture-prone plaques in apolipoprotein E gene-deficient mice. The protective effect of LEO for stabilizing atherosclerotic plaques was due to improved collagen content, increased fibrous cap thickness, and decreased accumulation of macrophages/foam cells. So far, LEO has passed the safety and feasibility test of phase I clinical trial.

Brood success of sex-role-reversed pheasant-tailed jacanas: the effects of social polyandry, seasonality, and male mating order.

Multiple mating by avian females may increase hatching and overall brood success; however, reproductive effort and parental investment are costly, and females may be gradually depleted, with lowered outputs over time. Thus, males in social polyandry systems may differ greatly in their reproductive gains. In the present study, we investigated the reproductive outputs of social polyandrous and sex-role-reversed pheasant-tailed jacanas, Hydrophasianus chirurgus, to assess the effects of polyandry, seasonality, and male mating order on breeding success. Female jacanas produced multiple clutches, either by leaving two or more clutches with an individual male (22%), or by mating with two or more males (78%). The polyandrous females laid both the first and second clutches earlier and showed a breeding period more than twice as long as that of monandrous females. Both polyandry and seasonality affected the fate of a clutch, where clutches from polyandrous females and the early season had higher hatching and brood success rates, but the number of polyandrous females declined over the season. Polyandrous females not only laid more clutches and eggs, and gained more hatchlings and fledglings, but also achieved higher per-clutch outputs and hatching rates than monandrous females. In polyandry groups, males gained higher total hatchlings and fledglings, although not total clutches or eggs, than males in monandry or bi-andry groups. Moreover, males in polyandry groups achieved higher hatchlings and fledglings per clutch and higher hatching and brood success rates. In polyandry groups, the first-mating males obtained more clutches, eggs, and hatchlings; however, they did not have higher success rates, nor total fledglings and per-clutch outputs, than males who mated later. Overall, the results indicate a selective advantage of polyandry for the jacanas studied, particularly in the early breeding season. This advantage, however, differs both between the sexes and intra-sexually, suggesting strong connections with certain ecological/environmental conditions in addition to the jacanas' own quality.

Epstein-Barr virus-encoded LMP2A induces an epithelial-mesenchymal transition and increases the number of side population stem-like cancer cells in nasopharyngeal carcinoma.

It has been recently reported that a side population of cells in nasopharyngeal carcinoma (NPC) displayed characteristics of stem-like cancer cells. However, the molecular mechanisms underlying the modulation of such stem-like cell populations in NPC remain unclear. Epstein-Barr virus was the first identified human tumor virus to be associated with various malignancies, most notably NPC. LMP2A, the Epstein-Barr virus encoded latent protein, has been reported to play roles in oncogenic processes. We report by immunostaining in our current study that LMP2A is overexpressed in 57.6% of the nasopharyngeal carcinoma tumors sampled and is mainly localized at the tumor invasive front. We found also in NPC cells that the exogenous expression of LMP2A greatly increases their invasive/migratory ability, induces epithelial-mesenchymal transition (EMT)-like cellular marker alterations, and stimulates stem cell side populations and the expression of stem cell markers. In addition, LMP2A enhances the transforming ability of cancer cells in both colony formation and soft agar assays, as well as the self-renewal ability of stem-like cancer cells in a spherical culture assay. Additionally, LMP2A increases the number of cancer initiating cells in a xenograft tumor formation assay. More importantly, the endogenous expression of LMP2A positively correlates with the expression of ABCG2 in NPC samples. Finally, we demonstrate that Akt inhibitor (V) greatly decreases the size of the stem cell side populations in LMP2A-expressing cells. Taken together, our data indicate that LMP2A induces EMT and stem-like cell self-renewal in NPC, suggesting a novel mechanism by which Epstein-Barr virus induces the initiation, metastasis and recurrence of NPC.

The chronic effects of oil pollution on marine phytoplankton in a subtropical bay, China.

To evaluate the effects of crude oil water accommodated fraction (WAF) on marine phytoplankton community, natural phytoplankton collected seasonally from the Yueqing bay were exposed to eight groups of crude oil WAF for 15 days under laboratory conditions. Chlorophyll a and cell density were measured, and species of phytoplankton were identified every 24 h to reflect the change of phytoplankton community. The results showed that (1) High concentrations (≥ 2.28 mg l(-1)) of oil pollution would greatly restrain phytoplankton growth (p<0.001), decrease chlorophyll a content and cell density, whereas low concentrations (≤ 1.21 mg l(-1)) did not restrain its growth but rather promoted the phytoplankton growth. (2) The biodiversity, evenness, and species number of phytoplankton were all significantly influenced by crude oil WAF in all seasons (p<0.001). (3) The dominant species changes were different under different pollutant concentrations in different seasons. Different species had different tolerances to the oil pollution, thus leading to abnormal succession.

Author Correction: Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys.

Following the publication of our paper (Zhang et al., 2020), it has come to our attention that we erroneously listed two funding sources unrelated to this study in the "ACKNOWLEDGEMENTS" section. Hereby, we wish to update the "ACKNOWLEDGEMENTS" section as a correction.

The role of concurrent chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma among endemic population: a meta-analysis of the phase III randomized trials.

BACKGROUND: The main objective of this meta-analysis was to determine the clinical benefit of concurrent chemoradiotherapy (CCRT) compared with radiation alone (RT) in the treatment of nasopharyngeal carcinoma (NPC) patients in endemic geographic areas. METHODS: Using a prospective meta-analysis protocol, two independent investigators reviewed the publications and extracted the data. Published randomized controlled trials (RCTs) in which patients with NPC in endemic areas were randomly assigned to receive CCRT or RT alone were included. RESULTS: Seven trials (totally 1608 patients) were eligible. Risk ratios (RRs) of 0.63 (95% CI, 0.50 to 0.80), 0.76 (95% CI, 0.61 to 0.93) and 0.74 (95% CI, 0.62 to 0.89) were observed for 2, 3 and 5 years OS respectively in favor of the CCRT group. The RRs were larger than that detected in the previously reported meta-analyses (including both endemic and non-endemic), indicating that the relative benefit of survival was smaller than what considered before. CONCLUSIONS: This is the first meta-analysis of CCRT vs. RT alone in NPC treatment which included studies only done in endemic area. The results confirmed that CCRT was more beneficial compared with RT alone. However, the relative benefit of CCRT in endemic population might be less than that from previous meta-analyses.

Bleomycin induces upregulation of lysyl oxidase in cultured human fetal lung fibroblasts.

AIM: To investigate the mechanism of bleomycin (BLM)-induced pulmonary fibrosis. METHODS: Cultured human fetal lung fibroblast (HLF) cells were exposed to bleomycin (BLM) at 0-30 microg/mL for 24 h. Western blot analysis was used to detect lysyl oxidase (LO) protein expression. Real-time RT-PCR was used to detect LO mRNA level. LO catalytic activity was measured using diaminopentane as a substrate and Amplex red as a hydrogen peroxide probe. Copper (Cu) concentration was detected by flame atomic absorption spectrophotometry. RESULTS: Exposure of HLF cells to BLM at 10 microg/mL and 30 microg/mL increased LO catalytic activity to 130% and 158% of the control in the conditioned media. The expression of LO mRNA was increased to 5.5-fold of the control in HLF cells exposure to BLM at 3 microg/mL. BLM at 3 microg/mL also increased the expression of 46 kDa preproLO, 50 kDa proLO and 32 kDa mature LO to 219%, 130%, and 135% of the control, respectively. The Cu concentrations in conditioned media of cultured HLF cells exposed to BLM (10 and 30 microg/mL) were increased significantly to 1.48 and 2.46-fold of the control, respectively. CONCLUSION: Bleomycin induces upregulation of LO in cultured human fetal lung fibroblasts, which may be the mechanism of bleomycin-induced pulmonary fibrosis.

Aspirin inhibits proliferation of gemcitabine-resistant human pancreatic cancer cells and augments gemcitabine-induced cytotoxicity.

AIM: To investigate whether aspirin is able to augment gemcitabine-induced cytotoxicity in human pancreatic cancer cells. METHODS: Two gemcitabine-insensitive human pancreatic cancer cell lines, PANC-1 and Capan-1, were used. Cells were treated with either aspirin or gemcitabine alone or both of them. Cell growth and apoptosis were determined by MTT assay, Annexin V or Hoechest 33258 staining. Cell cycle distribution was examined by flow cytometry. Western blot with specific phosphorylated protein antibodies was used to detect the activation of protein kinase. RT-PCR and Western blot were applied to assess the transcription and protein level for cyclin D1 and Bcl-2. RESULTS: Aspirin alone significantly inhibits the proliferation of PANC-1 cells by causing cell cycle arrest at G(1) phase. Aspirin potentiates the anti-survival effect of gemcitabine as well as its pro-apoptotic effect in PANC-1 cells, although aspirin per se does not trigger apoptosis. Aspirin inhibits GSK-3beta activation and suppresses the expression of its downstream gene products (cyclin D1 and Bcl-2), which are implicated in proliferation, survival and chemoresistance of pancreatic cancer. The effects of aspirin on Capan-1, were similar to that on PANC-1. CONCLUSION: Our results suggest that aspirin inhibits the proliferation of gemcitabine-resistant pancreatic cancer cells and augments the antisurvival effect of gemcitabine, probably by suppressing the activity of GSK-3beta and its downstream gene products.

Characterization of a cancer stem cell-like side population derived from human pancreatic adenocarcinoma cells.

AIMS AND BACKGROUND: To identify and partially characterize the side population cells derived from three human pancreatic adenocarcinoma cell lines. METHODS: Side population cells were sorted from the human pancreatic adenocarcinoma cell lines SW1990, Capan-2, and BxPC-3 using flow cytometry and then analyzed for cell proliferation, clone formation, differentiation, chemoresistance, invasive potential, and tumorigenicity in a mouse model. RESULTS: Human pancreatic carcinoma cell lines SW1990, Capan-2, and BxPC-3 contain 2.7% +/- 0.35%, 3.6% +/- 1.2%, and 2.8% +/- 0.8% side population cells, respectively. We further investigated cancer stem cell characteristics with the moderately differentiated human pancreatic adenocarcinoma cell line SW1990. Flow cytometry analysis revealed that side population cells could differentiate into side population and non-side population cells and could exhibit differentiation potential. Using a clone formation assay, side population cells were shown to have a higher proliferation than non-side population cells. Compared to non-side population cells, side population cells were also more resistant to gemcitabine, a commonly used anti-cancer agent against pancreatic carcinoma, and were more invasive. Importantly, the CD133 level in side population cells was significantly higher than that in non-side population cells. The enhanced tumorigenecity was further confirmed in a male diabetic/severe combined immunodeficiency mouse model. As few as 3 x 10(3) side population cells were sufficient to induce tumor formation in the mouse model, compared to 10(7) non-side population or unsorted cells. CONCLUSIONS: Side population cells isolated from human pancreatic adenocarcinoma cell lines harbor cancer stem cell-like properties that may be related to the invasive potential and therapeutic-resistance of pancreatic adenocarcinoma.

Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys.

Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys ( Macacafascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3ß,5,6ß-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.

Orphan nuclear receptor Nur77 is required for the differentiation of C6 glioma cells induced by cholera toxin.

AIM: To investigate a possible regulator gene involved in the cholera toxin-induced differentiation of rat C6 glioma cells. METHODS: The global changes in the mRNA expression pattern induced by cholera toxin were analyzed using gene chip microarray. The selected gene was then silenced by RNA interference or overexpressed with an ORF plasmid to determine its necessity in this process. RESULTS: Nur77, a member of the orphan nuclear receptor family (NR4A), was markedly up-regulated during the process of differentiation. Furthermore, RNAi of nur77 attenuated the induction effect of cholera toxin on C6 cells, whereas overexpression of nur77 led to similarly differentiated behavior, including morphologic and biomarker changes, as well as cell cycle arrest. CONCLUSION: Nur77 participated actively and essentially as an important regulator in the cholera toxin-induced differentiation of C6 cells.

Increased circulating CD31+/CD42- microparticles are associated with impaired systemic artery elasticity in healthy subjects.

BACKGROUND: Impaired artery elasticity has been found in various pathological conditions related to endothelial dysfunction. Recently, CD31+/CD42- microparticles (MPs) emerged as a marker of endothelial injury. Whether CD31+/CD42- MPs, generated under physiological conditions, are correlated with artery properties has not been reported. METHODS: We evaluated brachia-ankle pulse-wave velocity (baPWV) (n = 76) and C1 large-artery and C2 small-artery elasticity indices (n = 56), using noninvasive devices for pulse-wave analysis in a group of healthy persons. The number of circulating CD31+/CD427- MPs (n = 76) was measured by flow cytometric analysis. RESULTS: Circulating CD31+/CD42- MPs were positively correlated with values of baPWV (r = 0.371, P = .008) and with C1 large-artery and C2 small-artery elasticity indices (r = -0.294, P = .037; and r = -0.310, P = .027, respectively). Multivariate analysis identified CD31+/CD42- MPs as potent contributors to the development of impaired systemic artery elasticity. CONCLUSIONS: The level of circulating CD31+/CD42- MPs, an important biomarker of dysfunctional endothelium and vascular injury, is closely associated with impaired systemic artery elasticity in healthy subjects. The present study suggests that CD31+/CD42- MPs may be a novel surrogate marker for the clinical evaluation of vascular damage.

Downregulation of mitochondrial cyclooxygenase-2 inhibits the stemness of nasopharyngeal carcinoma by decreasing the activity of dynamin-related protein 1.

Cancer stem cells (CSCs) are a small subset of malignant cells, possessing stemness, with strong tumorigenic capability, conferring resistance to therapy and leading to the relapse of nasopharyngeal carcinoma (NPC). Our previous study suggested that cyclooxygenase-2 (COX-2) would be a novel target for the CSCs-like side population (SP) cells in NPC. In the present study, we further found that COX-2 maintained the stemness of NPC by enhancing the activity of mitochondrial dynamin-related protein 1 (Drp1), a mitochondrial fission mediator, by studying both sorted SP cells from NPC cell lines and gene expression analyses in NPC tissues. Using both overexpression and knockdown of COX-2, we demonstrated that the localization of COX-2 at mitochondria promotes the stemness of NPC by recruiting the mitochondrial translocation of p53, increasing the activity of Drp1 and inducing mitochondrial fisson. Inhibition of the expression or the activity of Drp1 by siRNA or Mdivi-1 downregulates the stemness of NPC. The present study also found that inhibition of mitochondrial COX-2 with resveratrol (RSV), a natural phytochemical, increased the sensitivity of NPC to 5-fluorouracil (5-FU), a classical chemotherapy drug for NPC. The underlying mechanism is that RSV suppresses mitochondrial COX-2, thereby reducing NPC stemness by inhibiting Drp1 activity as demonstrated in both the in vitro and the in vivo studies. Taken together, the results of this study suggest that mitochondrial COX-2 is a potential theranostic target for the CSCs in NPC. Inhibition of mitochondrial COX-2 could be an attractive therapeutic option for the effective clinical treatment of therapy-resistant NPC.

Expression, purification and molecular modeling of recombinant fibrinogenase [IV], a metalloproteinase from Deinakistrodon acutus venom.

A novel metalloproteinase, recombinant fibrinogenase IV (rFIV(a)), was expressed and purified from Deinakistrodon acutus venom. It was a single chain protein with an apparent molecular weight 27 kDa and an isoeletric point of pH 7.1. RFIV(a) cleaved preferentially the Aalpha-chain and also cleaved Bbeta, gamma-chains of fibrinogen when the incubation time was prolonged. The proteolytic activity was inhibited by EDTA, l-cysteine, and DTT, indicating rFIV(a) was a metalloproteinase requiring disulfide bonds for its activity. It kept above 85% of the initial activity from pH 4.5-11, showed an equal maximum activity at the temperature range from 30 to 50 degrees C, and was inactivated by Zn2+, Cu2+ and Cd2+. Homology modeling of rFIV(a) showed that two highly conserved disulfide bonds (Cys159-Cys164 and Cys117-Cys197) was maintained from its structure, and it exhibited the characteristic conserved motif H142E143XXH146XXGXXH152, whose three histidine residues were involved in binding of the catalytically essential zinc ion. This work demonstrates the expression, purification and characterization of recombinant fibrinogenase IV, which belongs to class P-I metalloproteinase from D. acutus venom.

Laparoscopic Common Bile Duct Exploration Versus Open Approach in Cirrhotic Patients with Choledocholithiasis: A Retrospective Study.

OBJECTIVE: To evaluate the safety and benefits of laparoscopic common bile duct exploration (LCBDE) compared with open approach (OCBDE) in cirrhotic patients. MATERIALS AND METHODS: Between January 2009 and December 2012, a total of 113 cirrhotic patients with choledocholithiasis underwent common bile duct (CBD) explorations in our department. There were two groups of patients: A:LCBDE (n = 61) and B:OCBDE (n = 52). Patients' demographic characteristics, surgical data, postoperative outcomes, and long-term results were retrospectively collected and analyzed. RESULTS: There were no significant differences between the two groups in the demographic characteristics or preoperative status. The transcystic approach was successfully performed in 52 (46.0%) patients (group A:34, group B:20), whereas choledochotomy was successful in 59 (54.0%) patients (group A:27, group B:32). The differences between group A and group B in terms of surgical time (124.9 ± 34.2 minutes versus 132.6 ± 48.6 minutes, P = .323), stone clearance rate (93.4% versus 94.2%, P > .05), short-term complication rate (9.8% versus 13.4%, P = .547), and recurrent stone rate (6.6% versus 5.8%, P > .05) were not statistically significant. However, group A suffered less blood loss [95 (60-200) mL versus 200 (90-450) mL, P < .001] and shorter length of hospital stay (4.7 ± 2.5 days versus 11.3 ± 3.1 days, P < .001) than group B. In the LCBDE group, 4 (6.6%) patients were converted due to heavy inflammation and severe adhesions. No mortality, biliary injury, or stricture occurred during follow-up. CONCLUSION: LCBDE can be safely performed in patients with Child-Pugh A or B cirrhosis and choledocholithiasis, with considerable efficiency, minimal short-term complications, and acceptable long-term outcomes. LCBDE has the advantages over open CBD exploration of less bleeding and reduced length of hospital stay.

Evolutionary trajectories of snake genes and genomes revealed by comparative analyses of five-pacer viper.

Snakes have numerous features distinctive from other tetrapods and a rich history of genome evolution that is still obscure. Here, we report the high-quality genome of the five-pacer viper, Deinagkistrodon acutus, and comparative analyses with other representative snake and lizard genomes. We map the evolutionary trajectories of transposable elements (TEs), developmental genes and sex chromosomes onto the snake phylogeny. TEs exhibit dynamic lineage-specific expansion, and many viper TEs show brain-specific gene expression along with their nearby genes. We detect signatures of adaptive evolution in olfactory, venom and thermal-sensing genes and also functional degeneration of genes associated with vision and hearing. Lineage-specific relaxation of functional constraints on respective Hox and Tbx limb-patterning genes supports fossil evidence for a successive loss of forelimbs then hindlimbs during snake evolution. Finally, we infer that the ZW sex chromosome pair had undergone at least three recombination suppression events in the ancestor of advanced snakes. These results altogether forge a framework for our deep understanding into snakes' history of molecular evolution.

[Tumor necrosis factor-alpha induces release of endothelial microparticles from human endothelial cells].

OBJECTIVE: The present study was designed to investigate whether Tumor necrosis factor (TNF)-alpha stimulates release of endothelial microparticles (EMPs) by human endothelial cells, and whether EMPs may serve as a promising marker for endothelial injury and dysfunction. METHODS: Human umbilical venous endothelial cells (HUVEC) were incubated with or without TNF-alpha for 24 hours at 37 degrees C. EMPs generated on the surface of HUVEC were observed with a scanning electron microscopy. The CD31 and CD51 positive EMPs in culture supernatants were measured by flow cytometer. RESULTS: Fewer vesicles were observed on cell surface of control group, in TNF-alpha-stimulated one, however, cells manifested a blebby surface (eruption phenomenon) and more vesicles on surface were observed. The levels of EMPs were significantly increased in TNF-alpha stimulated cells compared with controls [CD31 + EMP, (164 +/- 63)/1000 cells vs. (42 +/- 10)/1000 cells, P < 0.05; CD51 + EMP, (260 +/- 108)/1000 cells vs. (19 +/- 4)/1000 cells, P < 0.05]. CONCLUSION: TNF-alpha can stimulate HUVEC to release EMPs which may serve as a surrogate marker for endothelial injury and dysfunction.

Investigation of Various Types of Nanorods as Sensitive Surface-Enhanced Raman Scattering Substrates.

Core-shell-isolated nanorods can be used to amplify the signals of target cancer antigen molecules. Recent research has suggested that these nanorods feature surface-enhanced Raman scattering (SERS) signals superior to those of nanoparticles. In this study, nanorod geometrical models based on core-shell-isolated nanocapsule morphology were employed to analyze the scattered power density in three-dimensional spaces. Superior to the conventional cross-section field analysis method, the average scattered power density based method in this presentation could verify the enhancement effects from all possible positions on the nanorod surface. The numerical results in this study were also compared with the experimental results described in the literature. The resonance scattering power reached the maximal value when the radius of the Au/SiO2 and Ag/SiO2 nanorods was 20 nm. At an incident wavelength of 751 nm, the Au/SiO2 and Au/Al2O3 nanorods achieved maximal scattered power density when spacing d=30 nm. Conversely, the Au/TiO2 nanorods achieved maximum scattered power density when spacing d=40 nm. When the core was Au, nanorods with shell thickness h of 1 nm produced a resonant scattering intensity same as it by the nanorods without shells. The numerical results also indicated a stronger resonance peak when the incident ray illuminated the major-axis plane of the Au/SiO2 nanorods. When the incident ray illuminated the curvature plane of the nanorods, the resonance wavelength clearly shifted toward the UV wavelength range. The four Au/SiO2 nanorods with symmetric arrangement achieved the highest resonance peak when the nanorod spacing was 30 nm. This presentation can serve as a key reference for the design of core-shell-isolated nanorods as highly sensitive SERS substrates.

Characterization of a Synthetic Steroid 24-keto-cholest-5-en-3ß, 19-diol as a Neuroprotectant.

BACKGROUND: Neuroactive steroids represent promising candidates for the treatment of neurological disorders. Our previous studies identified an endogenous steroid cholestane-3ß, 5α, 6ß-triol (Triol) as a novel neuroprotectant. AIM: We aimed to identify a potent candidate for stroke treatment through a screening of Triol analogs. METHODS: Hypoxia- and glutamate-induced neuronal injury models in vitro, middle cerebral artery occlusion (MCAO)-induced cerebral ischemia model in vivo, fluorescein diacetate (FDA) for alive and propidium iodide (PI) for dead staining, LDH assay, and calcium imaging techniques were used. RESULTS: 24-keto-cholest-5-en-3ß, 19-diol (Diol) showed the most potent neuroprotective effect among the screened structurally related compounds. FDA and PI staining showed that Diol concentration dependently increased the survival rate of cerebellar granule neurons (CGNs) challenged with glutamate or hypoxia, with an effective threshold concentration of 2.5 µM. Consistently, the quantitative LDH release assay showed the same concentration-dependent protection in both models. Diol, at 10 µM, potently decreased glutamate- and hypoxia-induced LDH release from 51.6 to 18.2% and 62.1 to 21.7%, respectively, which values are close to the normal LDH release (~16-18%). Moreover, we found Diol effectively decreased MCAO-induced infarction volume in mice from ~23% to 7%, at a dose of 6 mg/kg. We further explored the underlying mechanism and found that Diol attenuated NMDA-induced intracellular calcium ([Ca(2+) ]i ) increase in cortical neurons, suggesting a negative modulatory effect on NMDA receptor. CONCLUSION: Taken together, we identified Diol as a potent neuroprotectant. It may represent a novel and promising neuroprotectant for stroke intervention.