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• Cerebral infarction is defined as death of the brain or retinal cells. • Neopterin levels were higher in stroke patientsand correlated with disease severity. • Neopterin can be a valuable marker of a multiple biomarker prognosis model. Neopterin is an inflammatory marker that is found to have prognostic value in cardiovascular diseases but its prognostic role in cerebrovascular diseases is not as clear. This study evaluates the prognostic role of neopterin in patients with ischemic stroke. Studies were identified after a literature search in electronic databases (Ovid, PubMed, Science Direct, and Wiley) and were selected based on precise eligibility criteria. Random-effects meta -analyses were performed to estimate mean difference in blood neopterin levels between ischemic stroke patients and healthy individuals or between severe and low/moderate ischemic stroke. Prognostic information contained in research articles of included studies was synthesized. Fourteen studies (1823 ischemic stroke patients and 2189 healthy individuals) were included. Serum neopterin levels were 4.22 ng/ml [95% confidence interval (CI): 3.66, 4.77] in ischemic stroke patients and 1.80 ng/ml [95% CI: 1.13, 2.46] in normal individuals (mean difference 2.14 ng/ml [95% CI: 1.41, 2.87]; p < 0.00001). Neopterin levels were significantly higher in patients with severe than in low/moderate ischemic stroke (mean difference 1.36 ng/ml [95% CI: 0.58, 2.13]; p = 0.0006). In individual studies, higher serum neopterin levels were found to be predictive of secondary stroke, adverse clinical or functional outcomes, depression, and mortality. Neopterin levels correlated positively with high-sensitivity c reactive protein (hsCRP), National Institutes of Health Stroke Scale score, and infarct volume. Blood neopterin levels are found significantly higher in ischemic stroke patients and correlated positively with hsCRP, disease severity, and infarct volume. Higher neopterin levels are associated with a worse prognosis of ischemic stroke. [ABSTRACT FROM AUTHOR]

Silymarin and Salvia miltiorrhiza are commonly used in various functional foods, daily herbal health supplements and food supplements for the treatment and prevention of liver disease. The aim of this study was to evaluate the herbal–drug interactions of silymarin and the aqueous extract of S. miltiorrhiza (AESM) on the pharmacokinetics of lamivudine in rat plasma as measured by liquid chromatography–tandem mass spectrometry (LC–MS/MS). A rapid and sensitive LC–MS/MS method was developed and validated according to the Food and Drug Administration (FDA) guidelines. Experimental rats were divided into the following four parallel groups: (1) lamivudine (10 mg/kg, i.v.) alone as a control group, (2) lamivudine (10 mg/kg, i.v.) + pretreated with silymarin (0.5 g/kg/day, p.o., daily for 5 days), (3) lamivudine (10 mg/kg, i.v.) + pretreated with AESM (1.0 g/kg/day, p.o., daily for 5 days), and (4) lamivudine (10 mg/kg, i.v.) + pretreated with silymarin (0.5 g/kg/day, p.o., daily for 5 days) + AESM (1.0 g/kg/day, p.o., daily for 5 days). The pharmacokinetic results demonstrate that AESM significantly increased lamivudine half-life (t 1/2 ), area-under concentration curve (AUC), and mean residence time (MRT), while clearance (CL) decreased. Thus, this study provides preclinical information regarding the pharmacokinetic interactions between lamivudine and the herbal health supplements. [ABSTRACT FROM AUTHOR]

Abstract: Neobavaisoflavone (NBIF) is an isoflavone isolated from Psoralea corylifolia L, a plant claimed to have osteogenic activity and used to treat bone fractures, osteomalacia and osteoporosis. The present results showed that NBIF concentration-dependently promoted osteogenesis in MC3T3-E1cells, demonstrated by notable enhancement of alkaline phosphatase (ALP) activity, increase of bone-specific matrix proteins expression including type I collagen (Col-I), osteocalcin (OCN) and bone sialoprotein (BSP), and formation of bone nodules. However, cell proliferation in the presence of NBIF was not affected. Results also demonstrated that NBIF up-regulated the expression of runt-related transcription factor 2 (Runx2) and Osterix (Osx), the bone-specific transcription factors participating in regulation of bone marker genes expression. Application of p38 inhibitor SB203580 repressed not only NBIF-induced activation of ALP, the expression of Col-I, OCN and BSP, but also the matrix proteins mineralization. Western blot analysis further revealed that NBIF increased the phosphorylated level of p38 concentration-dependently. Additionally, inhibition of p38 abolished the stimulatory effect of NBIF on the expression of Runx2 and Osx. Taken together, the osteogenic activity of NBIF might probably act through activation of p38-dependent signaling pathway to up-regulate the mRNA levels of Runx2 and Osx then stimulate bone matrix proteins expression. The beneficial effect of NBIF on mineralization demonstrated that NBIF represented as an active component existed in P. corylifolia and might be a potential anabolic agent to treat bone loss-associated diseases. [Copyright &y& Elsevier]

Abstract: Objectives: to evaluate maternal labour pain, fatigue, duration of the second stage of labour, the women''s bearing-down experiences and the newborn infant Apgar scores when spontaneous pushing is used in an upright position. Design: quasi-experimental study. Setting: medical centre in Taichung, Taiwan. Participants: 66 women giving birth at the hospital, with 33 primigravidas assigned to each group. Interventions: during the second stage of labour, the women in the experimental group pushed from an upright position and were given support to push spontaneously; the women in the control group pushed from a supine position and were supported via Valsalva pushing. Outcome measures: pain scores were recorded at two evaluation time points: at 10cm of cervical dilation and one hour after the first pain score evaluation. One to four hours after childbirth, the trained nurses collected the fatigue and pushing experience scores. Findings: the women in the experimental group had a lower pain index (5.67 versus 7.15, p=0.01), lower feelings of fatigue post birth (53.91 versus 69.39, p<0.001), a shorter duration of the second stage of labour (91.0 versus 145.97, p=0.02) and more positive labour experiences (39.88 versus 29.64, p<0.001) compared with the control group. There was no significant difference in the Apgar score for newborn infants during either the first minute (7.70 versus 7.73, p=0.72) or the fifth minute (8.91 versus 8.94, p=0.64). Key conclusions: the pushing intervention during the second stage of labour lessened pain and fatigue, shortened the pushing time and enhanced the pushing experience. Implications for practice: pushing interventions can yield increased satisfaction levels for women giving birth. [Copyright &y& Elsevier]

Abstract: Silymarin, which is extracted from the milk thistle (Silybum marianum), has been used for centuries for treating hepatic disorders and its hepatoprotective effects have been known for hundreds of years. Silymarin is a mixture of polyphenoic flavonoids, which include silibinin (silybin A and silybin B), isosilyin A and B, silychristin A and B, silydianin and other phenol compounds. The pharmacokinetics of silibinin shows fast absorption and elimination. Silymarin undergoes phase I and phase II metabolism, especially phase II conjugation reactions, it undergoes multiple conjugation reactions, and is primarily excreted into bile and urine. Silymarin has a good safety profile, but little is known regarding its potential for drug interaction. Silymarin has limited effect on the pharmacokinetics of several drugs in vivo; despite silymarin decreasing the activity of cytochrome P-450 (CYPs) enzymes, UDP-glucuronosyltransferase (UGT) enzyme, and reducing P-glycoprotein (P-gp) transport. Health-care practitioners should caution patients against co-administration of silymarin and pharmaceutical drugs. [Copyright &y& Elsevier]

Abstract: The aim of the present study was to investigate the effect of (−)-epigallocatechin-3-gallate (EGCG) on the pharmacokinetics of irinotecan (CPT-11) and its metabolite SN-38. EGCG was potentially used to modulate the ATPase activity of P-glycoprotein (P-gp). Experimental Sprague–Dawley rats were treated with EGCG (20mg/kg, i.v.) 10min before CPT-11 (10mg/kg, i.v.) administration, whereas the control group received CPT-11 (10mg/kg, i.v.) only. The biological samples were prepared by the protein precipitation and detected by HPLC-fluorescence detection which provided a good separation of CPT-11 and SN-38 within 10min. The pharmacokinetic data indicate that the area under the plasma concentration–time curves (AUC) of CPT-11 and SN-38 were increased by 57.7 and 18.3%, and AUC in bile were decreased by 15.8 and 46.8%, respectively, for the group pretreated with EGCG. The blood to bile distribution ratio (AUCbile/AUCblood) was significantly reduced after group coadministration of EGCG, it can be seen that the bile efflux transport system of CPT-11 and SN-38 may be markedly reduced by the treatment of EGCG which plays the role of P-gp inhibitor. In conclusion, EGCG was found to inhibit the transport of CPT-11 and SN-38 into the biliary elimination and their half-lives in plasma could be substantially prolonged. Based on the food–drug interaction, persons taking daily nutritional supplements should be warned of this interaction possibility. [Copyright &y& Elsevier]

Abstract: The extract of Evodia rutaecarpa fruit and its preparation were used for the treatment of gastrointestinal disorders and headache. To assess the possible herb–drug interaction, the ethanol extract of Evodia rutaecarpa fruit (1 and 2g/kg/day, p.o.) and the herbal preparation Wu-Chu-Yu-Tang (1 and 5g/kg/day) were given to rats daily for three consecutive days and on the fourth day theophylline was administered (2mg/kg, i.v.). Theophylline concentration in blood was measured by a microdialysis coupled to a liquid chromatographic system. Pharmacokinetic data were calculated by noncompartmental model. The results indicate that the theophylline level was significantly decreased by the pretreatment with the extract of Evodia rutaecarpa and herbal preparation Wu-Chu-Yu-Tang with dose-related manner. It is suggested that the herb–drug interaction may occur through the induction of the metabolism of theophylline. [Copyright &y& Elsevier]

Two plumbagic acid glucosides, 3′-O-β-glucopyranosyl plumbagic acid and 3′-O-β-glucopyranosyl plumbagic acid methylester along with five naphthoquinones (plumbagin, chitranone, maritinone, elliptinone and isoshinanolone), and five coumarins (seselin, 5-methoxyseselin, suberosin, xanthyletin and xanthoxyletin) were isolated from the roots of Plumbago zeylanica. All coumarins were not previously found in this plant. Cytotoxicity of these compounds to various tumor cells lines was evaluated, and plumbagin significantly suppressed growth of Raji, Calu-1, HeLa, and Wish tumor cell lines. [Copyright &y& Elsevier]

The effects of timosaponin A-III (TA-III), from Rhizoma Anemarrhenae, on Ca2+ mobilization in vascular endothelial cells and smooth muscle cells and on vascular tension have been explored. TA-III increased intracellular Ca2+ concentrations ([Ca2+]i) in endothelials cells at a concentration larger than 5 μM with an EC50 of 15 μM, and increased [Ca2+]i in smooth muscle cells at a concentration larger than 1 μM with an EC50 of 8 μM. Within 5 min, the [Ca2+]i signal was composed of a gradual rise, and the speed of rising depended on the concentration of TA-III. The [Ca2+]i signal was abolished by removing extracellular Ca2+ and was recovered after reintroduction of Ca2+. The TA-III-induced [Ca2+]i increases in smooth muscle cells were partly inhibited by 10 μM nifedipine or 50 μM La3+, but was insensitive to 10 μM verapamil and diltiazem. TA-III (10–100 μM) inhibited 0.3 μM phenylephrine-induced vascular contraction, which was abolished by pretreatment with 100 μM Nω-nitro-L-arginine (L-NNA) or by denuding the aorta. TA-III also increased [Ca2+]i in renal tubular cells with an EC50 of 8 μM. Collectively, the results show for the first time that TA-III causes [Ca2+]i increases in the vascular system. TA-III acted by causing Ca2+ influx without releasing intracellular Ca2+. TA-III induced relaxation of phenylephrine-induced vascular contraction via inducing release of nitric oxide from endothelial cells. [Copyright &y& Elsevier]

Background: Boschniakia rossica is a well-known traditional Chinese medicine for tonifying kidney and improving impotence. Boschnaloside is the major iridoid glycoside in this herb but therapeutic benefits for diabetes remained to be evaluated.Hypothesis/purpose: The current investigation aims to study the antidiabetic effect and the underlying pharmacological mechanisms.Study Design and Methods: Receptor binding, cAMP production, Ins secretion, glucagon-like peptide 1 (GLP-1) secretion, and dipeptidyl peptidase-4 activity assays were performed. Therapeutic benefits of orally administrated boschnaloside (150 and 300 mg/kg/day) were evaluated using severely 12-week old female diabetic db/db mice (Hemoglobin A1c >10%).Results: Oral treatment of boschnaloside for 4 weeks improved diabetic symptoms including fasting blood sugar, hemoglobin A1c, glucose intolerance, and Homeostatic Model Assessment of Ins Resistance, accompanied by circulating GLP-1active and adiponectin levels. In addition, bochnaloside treatment improved islet/β cell function associated with an alteration of the pancreatic and duodenal homeobox 1 level. It was shown that boschnaloside interacted with the extracellular domain of GLP-1 receptor and enhanced glucose stimulated Ins secretion. Boschnaloside also augmented the insulinotropic effect of GLP-1. Finally, the presence of boschnaloside caused a reduction of dipeptidyl peptidase-4 activity while enhanced GLP-1 secretion from STC-1 cells.Conclusion: It appears that bochnaloside at oral dosage greater than 150 mg/kg/day exerts antidiabetic effects in vivo through modulating the action of GLP-1. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Metabolic syndrome and vascular dysfunction was suggested to be the risk factors for Alzheimer's disease (AD). Xuefu Zhuyu decoction (XZD) is a traditional Chinese medicine used to treat metabolic syndrome and cardiac-cerebral vascular disease. The effects of XZD on ameliorating metabolic syndrome, amyloid-related pathologies and cognitive impairment in an animal model of AD with metabolic stress was investigated. Materials and method The animal model of AD with metabolic stress was created by administrating high-fat diet and a low-dose injection of streptozotocin prior to the appearance of senile plaques in APP/PS1 transgenic mice. The diabesity-associated metabolic changes and AD-related pathological alterations were examined. Results We found that XZD reduced body weight, insulin and leptin level, HOMA-IR, hepatic triglyceride, serum Aβ42 in the metabolic stressed AD animal. XZD also ameliorated oral glucose tolerant, Aβ deposition, astrocyte and microglia activation in the vicinity of plaques, and nesting behavior in the metabolic stressed AD animal. Conclusion The results of this study suggest that XZD is able to reduce the peripheral metabolic stress-mediated vascular hypoperfusion, neuroinflammation and AD-related pathology in APP/PS1 mice. [ABSTRACT FROM AUTHOR]

• The transmittance of the hydrogel in visible light band is not much different from that of the human cornea. • The mechanical stiffness of the hydrogel can be enhanced after two-photon CXL. • The hydrogel's microstructure offers insights into the reasons about improvement in the mechanical stiffness. • The hydrogel materials may prove a good candidate for artificial cornea implants. Corneal disease seriously threatens the quality of human vision and even causes blindness, but the shortage of corneal donors is insufficient to meet the demand for corneal transplantation. Artificial corneas prepared by hydrogel materials have the characteristics of high-water content, good biocompatibility and low cytotoxicity, is an effective way to treat corneal diseases. Although hydrogel technology has advanced over the past few years, their application often suffers from limitations in mechanical properties and complicated fabrication procedures. Here, a novel high-transparent and stiffness-enhanced bio-adhesive hydrogel composed of porcine type I collagen is developed by near infrared femtosecond laser based two-photon collagen crosslinking (CXL). Transmission spectra show that the transparency of the prepared hydrogel in the visible band is not less than 90 %, and the mechanical stiffness can be enhanced by 265.27 % ± 27.08 % without significantly reducing transparency after two-photon CXL. Additionally, the hydrogel's microstructure offers insights into the reasons contributing to the observed improvement in the mechanical stiffness. Overall, this work presents a generalizable preparation strategy for hydrogel materials with high light transmission, mechanical strength, and also potential of biocompatibility and bioadhesion in terms of biocompatibility, that might be an excellent candidate for artificial cornea implants and will foster potential advances in soft materials. [ABSTRACT FROM AUTHOR]

A preventive vaccine against hepatitis C virus (HCV) infection remains unavailable and newly developed drugs against viral replication are complicated by potential drug-resistance and high cost. These issues justify the need to develop alternative antiviral agents and expand the scope of strategies for the treatment of hepatitis C, such as targeting viral entry. In this study, we explore the bioactivity of Limonium sinense ( L. sinense ) and its purified constituents against HCV life cycle using subgenomic replicon and infectious HCV culture systems. Data indicated that the water extract from the underground part of L. sinense (LS-UW) exhibited potent inhibitory activity against HCV at non-cytotoxic concentrations. LS-UW targeted early HCV infection without affecting viral replication, translation, and cell-to-cell transmission, and blocked viral attachment and post-attachment entry/fusion steps. Bioactivity analysis of major constituents from LS-UW through viral infectivity/entry assays revealed that gallic acid (GA) also inhibits HCV entry. Furthermore, both LS-UW and GA could suppress HCV infection of primary human hepatocytes. Due to their potency and ability to target HCV early viral entry, LS-UW and GA may be of value for further development as prospective antivirals against HCV. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Gentiopicroside (GPS) is a secoiridoid glucoside isolated from the ethanol extract of Gentianae Radix with a content of 13%, which has been used for centuries in Chinese as a digestive aid. Aim of the study: This study investigates the pharmacokinetics of GPS and its metabolic pathway for the liver ischemia/reperfusion (I/R) in rats. Materials and methods: The experimental animals were anesthetized intraperitoneally (i.p.) with a mixture of urethane (1.0g/kg) and α-chloralose (0.1g/kg). A midline laparatomy was performed and the liver hilum was gently exposed. All structures in the portal triad (hepatic artery, portal vein, and bile duct) to the left and median liver lobes were occluded with silk thread for 30min. Ischemia was followed by a sudden reperfusion after removing the occluding threads. After 60min reperfusion, the rats received a single intravenous 5mg/kg dose of GPS. Results: The area under concentration curve (AUC) was significantly increased; however, the clearance (Cl) was significantly decreased in the liver I/R rats. Furthermore, after pretreated with SKF-525A (50mg/kg, i.p.), a cytochrome P450 (CYP) inhibitor, AUC, elimination half-life (t 1/2) and the mean residence time (MRT) of GPS in rat blood were significantly increased, suggesting that CYP was involved in the metabolism of GPS. For the group without liver I/R, GPS was administered at doses of 5mg/kg and 100mg/kg intravenously and orally, respectively. The pharmacokinetic results indicated that the AUC was 565±95.1 and 1163±273minμg/mL and the t 1/2 of GPS was 71±9 and 106±17 min after intravenous and oral administration, respectively. The oral bioavailability of GPS was 10.3±2.4% in the rats. Conclusions: The status of I/R might prolong the disposition of GPS, and the plasma concentration of GPS in the liver I/R injury rats was significantly increased. The increased body exposure of GPS in the treatment of liver I/R may result from the decreased metabolism of GPS mediated by CYP in the liver. [Copyright &y& Elsevier]

Abstract: Curcumin has considerable neuro-protective and anti-cancer properties but is rapidly eliminated from the body. By optimizing the HPLC method for analysis of curcumin, this study evaluates how the ability of curcumin to penetrate organs and different regions of the brain is affected by nanoparticulation to increase curcumin circulation time in the body. Curcumin-loaded PLGA nanoparticles (C-NPs) were prepared by the high-pressure emulsification-solvent evaporation method. The mean particle size and entrapment efficiency were 163nm and 46.9%, respectively. The release profile of C-NPs was an initial burst effect followed by sustained diffusion. In distribution studies, curcumin could be detected in the evaluated organs, including liver, heart, spleen, lung, kidney and brain. C-NPs were found mainly in the spleen, followed by the lung. Formulation significantly raised the curcumin concentration in these organs with increases in the AUC, t 1/2 and MRT of curcumin, though this was not apparent in the heart. Curcumin and C-NPs could cross the blood–brain barrier (BBB) to enter brain tissue, where it was concentrated chiefly in the hippocampus. Nanoparticulation significantly prolonged retention time of curcumin in the cerebral cortex (increased by 96%) and hippocampus (increased by 83%). These findings provide further understanding for the possible therapeutic effects of curcumin and C-NPs in further pre-clinical and clinical research. [Copyright &y& Elsevier]

Abstract: The orientation of the dipole moment, which is one of the important parameters in single-molecule fluorescence spectroscopy and often influenced by subtle changes in the local environment, is determined by highly focused generalized cylindrical vector beams combined with a confocal far-field microscope. As compared to the case of a radially polarized incident beam, the numerical results demonstrate that fluorescence intensity difference among single molecules with different orientations can be effectively overcome for a particular polarization direction of the generalized cylindrical vector beam, which may increases the signal-to-noise ratio of the practical experiments and then ease the difficulty in orientation determination of single molecules. [Copyright &y& Elsevier]

Abstract: Pharmacokinetics of free-form levobupivacaine (LB) and free-form racemic bupivacaine (BU) using microdialysis sampling technique were conducted in this study. Three microdialysis probes were implanted in the jugular vein toward the right atrium, brain striatum and bile duct of male Sprague–Dawley rats for concurrently sampling free drug. Effects of P-glycoprotein (P-gp) on the brain distribution and hepatobiliary excretion of LB and BU were examined for the first time after cyclosporine (CsA) administration. LB and BU in samples were determined by HPLC. The blood pharmacokinetics of free LB and free BU were not significantly different. For brain pharmacokinetics, the CsA pretreatment raised significantly the area under curve (AUC) of BU (24.0±5.9 vs. 14.6±4.4minμg/mL, p =0.015). Brain regions concentrations of LB and BU were significantly higher than plasma concentrations of LB (p <0.001) and BU (p <0.001), respectively. The BU concentration of cerebral cortex was significant higher than that of striatum (6.06±1.03 vs. 4.04±0.90μg/mL, p =0.005) and hippocampus (6.06±1.03 vs. 4.45±1.07μg/mL, p =0.04), suggesting that BU might display an uneven brain distribution. For bile pharmacokinetics, LB and BU went through hepatobiliary excretion, and the AUC of BU was significantly higher than that of the LB group (6.6±1.0 vs. 4.6±0.6minμg/mL, p =0.005). In addition, the pretreatment of CsA significantly reduced the hepatobiliary excretion of BU in terms of AUC (4.4±0.8 vs. 6.6±1.0minμg/mL, p =0.003). Furthermore, the maximum concentration (C max) of BU diminished significantly as a result of the CsA pretreatment (0.10±0.03 vs. 0.20±0.05μg/mL, p =0.002). To sum up, enantioselective brain distribution and hepatobiliary excretion of free LB and free BU were observed, and P-gp may relate to the drug transport. [Copyright &y& Elsevier]

• The spectral domain Z-scan method is proposed in this paper, which is insensitive to the sample's roughness and defects. • The spectral broadening caused by self-phase modulation (SPM) is used to evaluate material's nonlinear refractive index n 2. • This method can characterize the nonlinear optical properties of highly scattering materials, including biological samples and advanced materials, such as transparent colorful ceramics and unpolished perovskite. Characterizing the nonlinear optical properties of various materials plays a prerequisite role in nonlinear optics. Among different measurement methods, the well-known Z-scan technique and the modified versions have been recognized as simple and accurate methods for measuring both the real and imaginary parts of the nonlinear refractive index. However, the Z-scan methods based on detecting small beam variations impose a severe restriction on the roughness of materials. Therefore, measuring nonlinear optical properties of highly scattering media still remain challenging. Inspired by the innovation of the conventional Z-scan method that replaces the measurement of the wavefront phase shift by measuring the spatial pattern in the far-field, the spectral domain Z-scan technique is presented in this paper. It has the great potential in characterizing the nonlinear refractive index of highly scattering medium, since the scattering efficiency is insensitive to the wavelength for Mie scattering, which occurs for wavelengths far smaller than the roughness. Moreover, to demonstrate the advantages of the spectral domain Z-scan technique, the nonlinear refractions of polished slides and frosted slides were measured, which agree well with previous reports. [ABSTRACT FROM AUTHOR]

Abstract: Chemical examination of the n-BuOH extract from the aerial parts of Epimedium sagittatum led to isolation of three prenylated flavonol glycosides sagittasine A–C, two acylated flavonol glycosides kaempferol-3-O-(2″-E-p-coumaroyl,4″-Z-p-coumaroyl)-α-l-rhamnopyranoside and kaempferol-3-O-(3″-Z-p-coumaroyl,4″-E-p-coumaroyl)-α-l-rhamnopyranoside, together with known flavonoids, flavonolignans, 2-phenoxychromones, a lignan, and aromatic acid derivatives. Flavonolignans were identified for the first time in this plant. The vasorelaxing properties of the n-BuOH extract of E. sagittatum and 13 isolated compounds were tested using pre-contracted rat aorta rings in an organ bath apparatus. The results indicated that the n-BuOH extract of E. sagittatum produced a partial endothelial nitric oxide-dependent vasorelaxation, with EC50 of 0.16±0.03mg/ml. However, the 13 compounds tested, generated only a mild or moderate relaxation, and did not possess significant vasorelaxing effect individually. [Copyright &y& Elsevier]

The effects of Cordyceps cicadae extracted fractions on human mononuclear cells (HMNC) proliferation were determined by tritiated thymidine uptake. The results indicated that aqueous methanol (50%) extracts of C. cicadae ascocarps portion (CC-1-2) enhanced HMNC proliferation activated with phytohemagglutinin (PHA) with an EC50 of 13.8±4.6 μg/ml. By contrast, the methanol (100%) extracts of C. cicadae insect-body portion (CC-2-1) suppressed HMNC proliferation stimulated by PHA with an IC50 of 32.5±5.2 μg/ml. Cell viability test indicated that inhibitory effects of CC-2-1 on HMNC proliferation were not through direct cytotoxicity. The action mechanisms of CC-1-2 and CC-2-1 may involve the regulation of interleukin-2 (IL-2) and interferon-γ (IFN-γ) production in HMNC. Since CC-2-1 suppressed IL-2 and IFN-γ production in HMNC induced with PHA. The CC-1-2 enhanced IL-2 and IFN-γ production of HMNC stimulated with PHA in a concentration dependent manner. Therefore, the results demonstrated that C. cicadae contained growth modulators for HMNC. [Copyright &y& Elsevier]

Hepatitis D virus (HDV), which co-infects or superinfects patients with hepatitis B virus, is estimated to affect 74 million people worldwide. Chronic hepatitis D is the most severe form of viral hepatitis and can result in liver cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Currently, there are no efficient HDV-specific drugs. Therefore, there is an urgent need for novel HDV therapies that can achieve a functional cure or even eliminate the viral infection. In the HDV life cycle, agents targeting the entry step of HDV infection preemptively reduce the intrahepatic viral RNA. Human sodium taurocholate co-transporting polypeptide (hNTCP), a transporter of bile acids on the plasma membrane of hepatocytes, is an essential entry receptor of HDV and is a promising molecular target against HDV infection. Here, we investigated the effect of ergosterol peroxide (EP) on HDV infection in vitro and in vivo. EP inhibited HDV infection of hNTCP-expressing dHuS-E/2 hepatocytes by interrupting the early fusion/endocytosis step of HDV entry. Furthermore, molecular modeling suggested that EP hinders LHBsAg binding to hNTCP by blocking access to S267 and V263. In addition, we generated hNTCP-expressing transgenic (Tg) C57BL/6 mice using the Cre/loxP system for in vivo study. EP reduced the liver HDV RNA level of HDV-challenged hNTCP-Cre Tg mice. Intriguingly, EP downregulated the mRNA level of liver IFN-γ. We demonstrate that EP is a bona fide HDV entry inhibitor that acts on hNTCP and has the potential for use in HDV therapies. [Display omitted] • Ergosterol peroxide inhibits HDV entry into hepatocytes. • EP interferes with the fusion/endocytosis step of early HDV infection. • EP reduces HDV RNA levels in the liver of HDV-challenged hNTCP-Cre Tg mice. • EP is a human NTCP-targeted HDV entry inhibitor. • EP is identified as a potential therapeutic agent against HDV infection. [ABSTRACT FROM AUTHOR]

Highlights • The alcoholic liquids are observed by single beam time-resolved eclipsed Z-scan. • A simple method to extract the purely optical nonlinearities is presented. • The n 2 is 2.04 × 10−16 and 1.72 × 10−16 cm2/W for methanol and ethanol, respectively. • The self-focusing effects are masked by thermal effects after ∼10 μs irradiation. Abstract The experiments and applications of nonlinear optical liquids are often complicated by the presence and competition of the fast self-focusing and slow self-defocusing effects. As a result, the time-resolved measurements of liquids nonlinearities are very crucial. In this work, the temporal evolution of optical nonlinearities due to the accumulation of thermal effect for alcoholic liquids—frequently adpoted as the solvent of many organic nonlinear molecules and used in many nonlinear optical experiments—under high-repetition-rate femtosecond lasers is demonstrated using single beam time-resolved eclipsed Z-scan, that is, the combination of single beam time-resolved Z-scan and eclipsed Z-scan methods. The pure self-focusing nonlinearities arising from molecular reorientation of alcoholic liquids can be precisely extracted by a simple data processing. It can be concluded that the characteristic time of the accumulation of thermal nonlinear optical effects is 479.28 and 601.62 μs, and the fast self-focusing effects will be completely masked by the thermal nonlinear optical effects after t = 17.35 and 22.25 μs of laser irradiation for methanol and ethanol, respectively. The “combined” Z-scan technique can also have an extensive application for other advanced materials. [ABSTRACT FROM AUTHOR]

• Filament-induced aerosol fluorescence emission appears a strong angular dependence. • The backward angular distribution of the aerosol fluorescence can be attributed to Mie scattering. • The divergence angle of aerosol fluorescence radiation is affected by the particle size distribution. Backward angular distributions of the sodium fluorescence in NaCl aerosols induced by femtosecond laser filamentation in air with a distance of 10 m are measured. The recorded signals appear as strong angular dependence. Further study indicates that it could be associated with the Mie scattering of the filamentation-induced "aerosol lasing" in the forward direction. These results will benefit the remote-sensing of air pollutants by femtosecond laser filamentation-based LIDAR (light detection and ranging). [ABSTRACT FROM AUTHOR]

• Acoustic method was adopted to quantitatively measure the long-distance filamentation. • A simple physical model was presented to analyze the spatial distribution of filament. • The onset and length of filament can be conveniently obtained from the model. • The increase of the filament length can be obtained for longer pulse with more energy. The promising application of femtosecond laser filamentation in atmospheric remote sensing brings imperative demand for diagnosing and controlling the spatiotemporal dynamics of long-distance filamentation. Here, the acoustic method was adopted to quantitatively diagnose the long-distance filamentation of femtosecond pulses manipulated by energy and temporal domain. The onset and length of filament can be conveniently obtained from a simple analytic formula based on reasonable approximation and further demonstrated by the experimental results. The influence of pulse energy and initial pulse chirp under three different focal lengths (∼10 m, 20 m, and 30 m) on the filamentation in the air were studied experimentally. These findings provide a guiding significance for the optimal control of the long-distance propagation of filament, thereby laying a firm foundation for femtosecond laser-based atmospheric remote sensing. [ABSTRACT FROM AUTHOR]