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Introduction: Chronic myeloid leukemia (CML) is a chronic disease with treatment-free remission (TFR) increasingly regarded as a feasible goal of treatment. However, various factors may influence adherence to international guidelines for CML management. This study aimed to compare the reporting of care between patients with CML and their treating doctors. Methods: Parallel patient and physician online surveys were conducted between September 22, 2021, and March 15, 2022, which focused on the perceptions of 1882 adult patients with CML and 305 physicians regarding tyrosine kinase inhibitor (TKI) treatment options, monitoring and toxicities, TFR, and challenges faced. Results: Among the enrolled patients, 69.9% received first-line imatinib treatment, 18.6% received nilotinib, and 4.7% received dasatinib. Among the patients treated with imatinib, 36.7% switched to other TKIs due to imatinib resistance/intolerance (71.1%), exploration of more potent TKIs to achieve TFR (8.9%), and treating physicians’ recommendation (14.0%), with a median duration of initial treatment of 14 months [interquartile range (IQR) 6–36]. Most (91.8%) physicians agreed that the breakpoint cluster region–Abelson 1 (BCR::ABL1) transcript level should be assessed every 3 months, but only 42.7% of individuals committed to 3-monthly testing and only 17.8% strictly followed their treating physicians’ recommendation. Half of the patients aimed for TFR; however, just 45.2% of physicians considered TFR as one of the top three goals for their patients. The major concern in obtaining TFR was patients’ adherence. Fatigue was often distressing for patients with TKIs, while physicians were more concerned about platelet and neutrophil counts. A total of 12% and 20.8% of patients reported moderate/severe anxiety and depression, respectively, while only 53.7% of physicians had concerns about their patients’ mental health. During the coronavirus disease 2019 (COVID-19) pandemic, 69.2% of patients reported a reduction in their income. Among these patients, 61.8% maintained their current treatment, while 7.3% switched to cheaper alternatives or discontinued treatment, with over 80% of these patients belonging to the low-income group. Conclusions: Overcoming challenges in patient–physician communication and treatment access is key to improving disease management and quality of life, especially for patients with low income. Trial Registration: ClinicalTrials.gov identifier NCT05092048.

The promising application of femtosecond laser filamentation in atmospheric remote sensing brings imperative demand for diagnosing the spatiotemporal dynamics of filamentation. Acoustic emission (AE) during filamentation opens the door to giving insight into the dynamic evolution of filaments in air. In particular, the frequency features of the acoustic emission provide relevant information on the conversion of laser energy to acoustic energy. The acoustic emission of femtosecond laser filament manipulated by laser pulse energy and focal lengths was measured quantitatively using a broadband microphone. The experimental results showed that the acoustic power ${W}$ presents a squared dependence on the laser pulse energy ${E}$ , i.e. ${W} \propto {E} ^{2}$ . The spectral bandwidth of the acoustic pulse emitted from the optical filament is found to be an indicator of the filament intensity distribution, which is positively correlated with the laser filament intensity. These findings are helpful for studying the plasma filament properties and complex dynamic processes through acoustic diagnostics and benefit the remote applications of laser filament.

ABSTRACTRAB27B is a member of Ras-like small GTPases that plays a role in endocytosis, exocytosis, and vesicle trafficking. We made an attempt to study the impacts of RAB27B on the proliferation and apoptosis of acute myeloid leukemia (AML) cells. The silencing of RAB27B was induced by siRNA for the detection of proliferation, cell cycle, and apoptosis, respectively by Cell Counting Kit-8 (CCK8), flow cytometry, and TUNEL. Related markers were also evaluated by Western blot analysis. The interaction between RAB27B and BDH2 was predicted by bioinformatics analysis and determined by immunoprecipitation. The gain of function of BDH2 was also detected by these functional assays. RAB27B exhibited high levels in AML cells, and RAB27B silencing led to reduced proliferation, increased cell cycle arrest and apoptosis levels. Then, the interaction between RAB27B and BDH2 was confirmed. Moreover, the effects of RAB27B inhibition on the proliferation, cell cycle arrest, and cell apoptosis were abolished after BDH2 overexpression. RAB27B inhibits proliferation and promotes apoptosis of leukemic cells by interacting with BDH2. Targeting RAB27B might be an effective method for the treatment of AML.

Terahertz technology has shown broad prospects for measuring corneal water content, which is an important parameter of ocular health. Based on terahertz time-domain spectroscopy, a new indicator named characteristic ratio (CR) of the sum of low (0.2-0.7 THz) and high (0.7-1.0 THz) frequency spectral intensities, for characterizing corneal hydration is introduced in this work. CR is calculated from the real-time reflection spectra after error elimination of ex vivo human corneal stroma samples which is collected during dehydration under natural conditions (temperature: 22.4 ± 0.3°C; humidity: 20.0 ± 3%). The corresponding relationships between CR and corneal water content are reported. Comparing the linear fitting results with the published similar study, the coefficients of variation of the fitting slope and intercept are 39.4% and 27.6% lower, respectively. This indicates that this approach has the potential to achieve corneal water content in-vivo detection in the future.

Dietary fat has been suggested to be the cause of various health issues. Obesity, hypertension, cardiovascular disease, diabetes, dyslipidemia, and kidney disease are known to be associated with a high-fat diet (HFD). Obesity and associated conditions, such as type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD), are currently a worldwide health problem. Few prospective pharmaceutical therapies that directly target NAFLD are available at present. A Traditional Chinese Medicine, ginseng-plus-Bai-Hu-Tang (GBHT), is widely used by diabetic patients to control glucose level or thirst. However, whether it has therapeutic effects on fat-induced hepatic steatosis and metabolic syndrome remains unclear.

The purpose of the present study was to investigate the role of the methylation status of the DACT1 gene on the invasion and metastasis of nasopharyngeal carcinoma cells. The levels of methylation and expression of the DACT1 gene in nasopharyngeal carcinoma tissues and CNE2 cells were determined by methylation-specific PCR and RT-PCR, respectively. CNE2 cells were treated with 5-aza-2-deoxycytidine, and the variation in the methylation status of the DACT1 gene was detected, as well as the influence of methylation on invasiveness of nasopharyngeal carcinoma cells. The DACT1 gene was hyper-methylated in 44 of 62 cases of nasopharyngeal carcinoma. The DACT1 gene was hyper-methylated in 32 of 38 cases of nasopharyngeal carcinoma with lymph node metastasis, and the DACT1 gene was hyper-methylated in 7 of 24 cases of nasopharyngeal carcinoma without lymph node metastasis. The DACT1 mRNA level was weakly expressed or not expressed in all nasopharyngeal carcinoma tissues with hyper-methylated DACT1 genes; however, the DACT1 mRNA level was highly expressed in nasopharyngeal carcinoma tissues with low expression of the methylated DACT1 gene. The DACT1 gene was hyper-methylated and not expressed in CNE2 cells that did not have 5-aza-2-deoxycytidine treatment. After 5-aza-2-deoxycytidine treatment, the DACT1 gene was demethylated and the expression of DACT1 was restored. Moreover, the invasion ability was inhibited in CNE2 cells treated with 5-aza-2-deoxycytidine. The expression of DACT1 was related to the methylation status. High expression of DACT1 may inhibit the invasion and metastasis of nasopharyngeal carcinoma cells.

Three new labdane-type diterpenoids, 6α-O-isovalerylnidorellol (1), (12S)-blumdane (2), and (12R)-epiblumdane (3), and three new bisnorditerpenoids, 6α-O-(3-methyl-2-butenoyl)sterebin A (5), 6α-O-angeloylsterebin A (6), and 6α-O-isovalerylsterebin A (7), plus 17 known compounds were isolated from Blumea aromatica. Their structures of the new compounds were proposed by detailed spectroscopic analysis. The absolute configuration at C-12 of blumdane (2) was determined by the modified Mosher’s method. The anti-inflammatory and anti-immunosuppressive effects of these isolated compounds were assessed. Compounds 9, 16, and 23(at 40 μM) showed a slight suppression of TNF-α production, but no or little effect on the expression of PD-L1 in granulocytic myeloid-derived suppressor cells was observed for all test compounds.

Treatment of non-small cell lung cancer (NSCLC) is a high unmet medical need. We repurposed Suan-Zao-Ren-Tang (SZRT), a widely used traditional Chinese medicine in alleviating insomnia, to sensitize vinorelbine-induced anti-NSCLC effect and have unveiled the underlying mechanism. B7E2, the partial purified extract from SZRT, was used through bioactivity-guided fractionation based on anti-proliferative activity in NSCLC cell lines A549 and NCI-H460. Three batches of B7E2 and their individual components were prepared for the examination of components and bioactivity and mechanistic study. B7E2 alone had no cytotoxic effect but its combination with vinorelbine displayed a synergistic activity in killing NSCLC cells. Apoptotic sensitization was verified by a remarkable increase of caspase activation and phosphorylation of Bcl-2 and Bcl-xL. Combination treatment prolonged mitotic arrest and induced a substantial activation of spindle assembly checkpoint (SAC) characterized by BUBR1 phosphorylation at Ser670 and Thr680, and cyclin B1 upregulation. Combination treatment enhanced the interaction between mitotic checkpoint complex (MCC) components, including BUBR1, MAD2, BUB3 and CDC20. Further analysis revealed that SZRT components, including senkyunolide-A, trans-neocnidilide, 3-butylidenephthalide, betulinic acid and linoleic acid, were responsible for B7E2 activities. Three B7E2 batches showed a good chemical similarity and similar activities between batches. The data suggest that B7E2 is a potential chemosensitizer in potentiating vinorelbine-induced anti-NSCLC activity through amplification and prolongation of SAC activation.

Background:Patients with relapsed/ refractory (R/R) FLT3-internal tandem duplication positive (FLT3-ITD+) acute myeloid leukemia (AML) have limited treatment options and poor prognosis. Clifutinib is a novel, highly selective, oral FLT-3 inhibitor with potent activity against FLT3-ITD(+) leukemic models both in vitroand in vivo. This study is a first-in-human study of clifutinib, with the purpose of evaluating the safety, tolerability, efficacy, and pharmacokinetic (PK) profile in Chinese patients with R/R FLT3-mutated AML (NCT04827069).

Introduction:

Introduction:

Background: Traditional “3+7” intense chemotherapy (IC) regimen is the standard treatment backbone for fitness patients with newly diagnosed AML. The azacitidine plus venetoclax (AB) regimen has recently been recommended for elderly AML patients or those ineligible for IC treatment. However, neither the “3+7” IC nor “AB” regimen unmet the needs ofadequate safety and effectiveness, especially on aspects of early death and some subtypes of leukemia, such as M5, or with RUNX1, FLT3-ITD, TP53 mutation, or with MCL-1 up-expression. Chidamide, a novel oral histone deacetylase inhibitor, can overcome the upregulating of MCL-1 expression induced by venetoclax, and synergy with azacitidine and venetoclax induces apoptosis of acute myeloid leukemia cells. Azacitidine-Venetoclax -Chidamide (ABC) combination regimen had been successfully used for refractory relapsed AML and newly diagnosed AML-M5 by Prof. Bin Xu and Prof. Shengli Xue, respectively. Whether the ABC regimen can be comparable to the “3+7” IC regimen in newly diagnosed AML induction therapy is still unknown.

The breakdown and related bubble dynamics driven by femtosecond laser pulses in liquid are very critical for the optimization of laser parameters in the applications of medical laser and nano/micro-object manipulation. In this paper, we conduct systematic research on the bubble dynamics in methanol driven by a few successive femtosecond laser pulses under 1 kHz repetition rate. It is demonstrated that it is more probable for two or more successive pulses to induce optical breakdown than only a single pulse. A physical scenario of bubble dynamics from generation to evolution is presented for the successive femtosecond laser pulses interacting with a sample, which also give a reasonable explanation for such a phenomenon. Moreover, the effects of pulse energy and numerical aperture on the optical breakdown and bubble dynamics are investigated and well explained. It is hinted that the laser pulses with high repetition rate (the maximum typically not exceeding the megahertz level so that the cumulative effect of heat cannot be ignored) and low energy and the lens with a large numerical aperture may be an optimal choice for the precise control of the bubble and cutting.

The hypothesis of this study is that fisetin and phase II conjugated forms of fisetin may partly undergo biliary excretion. To investigate this hypothesis, male Sprague–Dawley rats were used for the experiment, and their bile ducts were cannulated with polyethylene tubes for bile sampling. The pharmacokinetic results demonstrated that the average area-under-the-curve (AUC) ratios (k(%) = AUCconjugate/AUCfree-form) of fisetin, its glucuronides, and its sulfates were 1:6:21 in plasma and 1:4:75 in bile, respectively. Particularly, the sulfated metabolites were the main forms that underwent biliary excretion. The biliary excretion rate (kBE(%) = AUCbile/AUCplasma) indicates the amount of fisetin eliminated by biliary excretion. The biliary excretion rates of fisetin, its glucuronide conjugates, and its sulfate conjugates were approximately 144, 109, and 823%, respectively, after fisetin administration (30 mg/kg, iv). Furthermore, biliary excretion of fisetin is mediated by P-glycoprotein.

Six new meroterpenoids, diplomeroterpenoids A–F (1–6), two new chalcone-lignoids, diplochalcolins A and B (7, 8), and 13 known compounds were isolated from the root extract of Mimosa diplotricha. Diplomeroterpenoids A–F consist of a 4H-chromen-4-one and a diterpenoid unit, and their absolute configurations were determined by X-ray crystallographic analysis. Compounds 1–3and 5showed potent inhibitory activity on protein farnesyl transferase, with IC50values from 5.0 to 8.5 μM. Compound 1showed antiproliferative activity against human hepatoblastoma HepG2 cells with a GI50value of approximately 8.6 μM.

An all-fiber modal interferometer based on a long period grating (LPG) inscribed in a two-mode photonic crystal fiber (PCF) and a slight core-offset spliced end is proposed and demonstrated. The LPG is fabricated to realize energy coupling from LP_01 core mode to LP_11 core mode, and the two core modes will interfere at the slight core-offset spliced end. We analyze the impact of energy coupling efficiencies of the LPG and the output spliced end on the extinction ratio of the interference fringes. With an appropriate energy coupling efficiency matching condition, our modal interferometer can realize lower insertion loss and high extinction ratio. Moreover, the sensitivities of our interferometer to strain and temperature are investigated, and the good stability of this device to external refractive index change is also demonstrated. As an all-fiber interferometer made of pure silica, this device has great potential applications in high temperature sensing fields, especially in harsh conditions.

Five new diaryldimethylbutane lignans, saurulignans A–E (1–5), four new tetrahydrofuran lignans, saurufurins A–D (6–9), and one arylnaphthalene lignan, saurunarin (10), were isolated from Saururus chinensis,along with 18 known compounds. Lignan 5showed significant inhibition of ADP-induced aggregation with an IC50value of 9.8 μM and AA-induced aggregation with an IC50value of 14.0 μM. Compound 19showed significant activity to inhibit PAF-induced aggregation with an IC50value of 9.1 μM. In addition, five isolated compounds could induce platelet aggregation. These results suggest that secondary metabolites in S. chinensishave bidirectional regulation on blood clotting and anticlotting effects.

In this paper, we present our study on the spectral discrimination between high and low quality tobacco leaves using a time-resolved ultraweak luminescence detection system. Photoinduced delayed luminescence (DL) is employed as a nondestructive and objective indicator of tobacco leaf quality. DL decay kinetics of tobacco leaf samples is measured, and the data are fitted by a hyperbolic cosecant function. Results show that the function’s parameter A is significantly related to the quality grades of tobacco leaves—compared with the low quality tobacco leaves, an increase of the A value by a factor of 7 is obtained for the high quality tobacco leaves. Research from this work contributes to the development of a novel optical method applicable for the quality evaluation of agricultural crops and food products.

The decay kinetic models of delayed luminescence of beans have been examined, the effect of the shape of bean samples on the properties of delayed luminescence has been investigated. It is showed the delayed luminescence of beans mainly comes from the surface of beans and can’t reflect the whole information of beans. After beans being crushed, the component of beans can be mixed together. When luminescence, the components of beans powders are all irradiated, which can reflect the whole information of beans. The fitting degree of hyperbolic function is best.

The effects of different lighting energy and different radiant power on the properties of delayed luminescence of beans were discussed. It is showed when lighting energy is from 2 to 25mJ, initial intensity A changes very much from 1200 to 8600. When lighting energy is from 200 to 600 mJ, initial intensity A has little change. Initial intensity A is in a linear relation with radiant power.

We propose a subwavelength B-shaped metallic hole array filter with an embedded thermally tunable InSb semiconductor bar in the terahertz regime. The resonance frequency of this filter can be actively tuned by controlling the temperature of InSb. The transmissions of the filter are calculated with the finite-difference time domain method at various temperatures. Narrowband THz wave with the full width at half maximum of 235 GHz can be selected in the frequency range from 0.74 to 2.02 THz at temperatures from 160 to 350 K.

In this work, photoinduced delayed luminescence (DL) was used to distinguish serum samples of patients with acute lymphoblastic leukemia from those of healthy volunteers. DL decay kinetics of human serum samples was measured using a homebuilt ultraweak luminescence detection system. It was found a significant difference in the weight distribution of the decay rate between normal and leukemic serum samples. A comparison of the DL kinetics parameters including the initial intensity, the peak decay rate, and the peak weight value was used in making discrimination between normal and leukemic human sera. Results in this work contribute to the development of a novel optical method for the early diagnosis of leukemia.

Bioassay-guided isolation of Mimosa diplotrichaled to the isolation of four new 5-deoxyflavones, diplotrins A–C (1–3) and diplotasin (4), together with 12 known flavonoids, flavonolignans, and triterpenoids. On the basis of spectroscopic evidence, compounds 1–4were characterized as 2′,5′-dihydroxy-3,7,8,4′-tetramethoxyflavone (1), 3′-hydroxy-3,7,8,4′-tetramethoxyflavone (2), 2′-hydroxy-7,4′,5′-trimethoxyflavone (3), and 4-hydroxy-3,10,11-trimethoxyisochromeno-[4,3-b]-chromen-7(5H)-one (4). The cytotoxic effects of these isolated compounds were evaluated against the A549, AGS, HT-29, and PC3 human cancer cell lines. Compounds 2and 5″-methoxyhydnocarpin-D (5) showed the most potent antiproliferative activity.

Silibinin is the main biologically active flavonolignan extracted from the seeds and fruits of milk thistle and has potential efficacy in the treatment of liver disease. The aim of the present study was to examine the hepatobiliary excretion of silibinin and its effect on dimethylnitrosamine (DMN)-induced liver cirrhosis. The experiments were divided into five groups: 10, 30, and 50 mg/kg silibinin alone, 30 mg/kg silibinin coadministered with cyclosporin A (CsA), and 50 mg/kg silibinin with liver cirrhosis induced by DMN. The data indicated that silibinin had dose-related pharmacokinetics in the dose ranges of 10 to 50 mg/kg. All of the unconjugated or total (unconjugated + conjugated) silibinin concentrations in the bile were significantly higher than those in plasma at the sampling time points at each dose, suggesting active hepatobiliary excretion. When coadministered with CsA, the area under the concentration versus time curve (AUC) in bile was significantly decreased. This result suggested that the active silibinin efflux might be partially inhibited by P-glycoprotein. In the DMN-induced liver cirrhotic rats, the AUC of plasma unconjugated silibinin was reduced by 53%; however, total silibinin was increased by 182%. These results together suggest that the phase II conjugative reaction of silibinin was blocked by treatment with DNM.

Theories to calculate the propagation of arbitrary-order correlations of stationary or nonstationary partially coherent electromagnetic fields are proposed. The theories are based on separated-coordinate mode decomposition, and can make the well-developed propagation theories of fully coherent electromagnetic fields applicable to partially coherent electromagnetic fields governed by linear Maxwell equations. The validity of the theories is illustrated by an example.

On the basis of the recently introduced definition of energy spectrum of a partially temporally coherent pulse train [Opt. Lett.29, 394 (2004)], we show that the well-known time-frequency uncertainty relationship applicable to a fully temporally coherent pulse train is still correct for a partially temporally coherent pulse train. The condition under which the uncertainty relationship reaches equality is derived. An example is presented to illustrate the validity of the uncertainty relationship.

Propagation theories of partially coherent electromagnetic fields based on coherent mode decomposition or separated-coordinate mode decomposition are proposed. With the proposed propagation theories, various powerful theories for the propagation of fully coherent electromagnetic fields can be used for the propagation of partially coherent electromagnetic fields. The proposed theories are applicable to any propagation problem of partially coherent electromagnetic fields governed by linear Maxwell equations. Some examples are provided to illustrate the validity of the proposed theories.

We report design theories of a diffractive superresolution element (DSE) to implement optical superresolution of focused partially spatially coherent laser beams. The design problem of the DSE can be transformed into a problem of linear programming to obtain a globally optimal solution. By using the design theories, some fundamental limits of optical superresolution of focused partially spatially coherent laser beams are proposed, and several design examples are provided. As expected, both the fundamental limits and the design examples show that worse spatial coherence will cause worse superresolution performance. The design theories provide a design approach with partially coherent beams and may be useful for other design problems under partially coherent illumination.

Theories of a technique for compression of an ultrashort femtosecond laser pulse beyond its Fourier-transform limit based on the pulse shaping technique are proposed. The technique is called superresolution in time domain (STD). Global optimization theories for the design of a mask to modulate the spectrum of an input pulse to obtain a STD output pulse are proposed. Several design examples illustrate the feasibility of STD. Some fundamental limits of STD are also provided.

Rapid production of reactive oxygen species (ROS) and upregulation of β2 integrin by leucocytes are two important inflammatory responses in human leucocytes. To evaluate whether three phenylpropanoid glycosides (acteoside, crenatoside, and rossicaside B) and two iridoid glucosides (boschnaloside and 8‐epideoxyloganic acid) identified from two medicinal plants with similar indications (Orobanche caerulescensand Boschniakia rossica) exhibited anti‐inflammatory activity, their effects on N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP) and phorbol‐12‐myristate‐13‐acetate (PMA)‐activated peripheral human neutrophils (PMNs) and mononuclear cells were examined. Pretreatment with 1–50 μmphenylpropanoid glycoside concentration‐dependently diminished PMA‐ and fMLP‐induced ROS production with IC50 values of approximately 6.8–23.9 and 3.0–8.8 μm, respectively. Iridoid glucoside was less effective than phenylpropanoid glycoside with an IC50 value of approximately 8.9–28.4 μmin PMA‐activated PMNs and 19.1–21.1 μmin fMLP‐activated mononuclear cells. Phenylpropanoid glycosides also effectively inhibited NADPH oxidase (NOX) and displayed potent free radical‐scavenging activity, but did not interfere with pan‐protein kinase C (PKC) activity. Furthermore, all compounds, except rossicaside B, significantly inhibited PMA‐ and fMLP‐induced Mac‐1 (a β2 integrin) upregulation at 50 μmbut not that of fMLP‐induced intracellular calcium mobilization. These drugs had no significant cytotoxicity as compared with the vehicle control. Our data suggested that inhibition of ROS production, possibly through modulation of NOX activity and/or the radical scavenging effect, and β2 integrin expression in leucocytes indicated that these compounds had the potential to serve as anti‐inflammatory agents during oxidative stress.

Rapid production of reactive oxygen species (ROS) and upregulation of β2 integrin by leucocytes are two important inflammatory responses in human leucocytes. To evaluate whether three phenylpropanoid glycosides (acteoside, crenatoside, and rossicaside B) and two iridoid glucosides (boschnaloside and 8-epideoxyloganic acid) identified from two medicinal plants with similar indications (Orobanche caerulescensand Boschniakia rossica) exhibited anti-inflammatory activity, their effects on N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol-12-myristate-13-acetate (PMA)-activated peripheral human neutrophils (PMNs) and mononuclear cells were examined. Pretreatment with 1–50 μmphenylpropanoid glycoside concentration-dependently diminished PMA- and fMLP-induced ROS production with IC50 values of approximately 6.8–23.9 and 3.0–8.8 μm, respectively. Iridoid glucoside was less effective than phenylpropanoid glycoside with an IC50 value of approximately 8.9–28.4 μmin PMA-activated PMNs and 19.1–21.1 μmin fMLP-activated mononuclear cells. Phenylpropanoid glycosides also effectively inhibited NADPH oxidase (NOX) and displayed potent free radical-scavenging activity, but did not interfere with pan-protein kinase C (PKC) activity. Furthermore, all compounds, except rossicaside B, significantly inhibited PMA- and fMLP-induced Mac-1 (a β2 integrin) upregulation at 50 μmbut not that of fMLP-induced intracellular calcium mobilization. These drugs had no significant cytotoxicity as compared with the vehicle control. Our data suggested that inhibition of ROS production, possibly through modulation of NOX activity and/or the radical scavenging effect, and β2 integrin expression in leucocytes indicated that these compounds had the potential to serve as anti-inflammatory agents during oxidative stress.

The protective effect of acteoside against membrane lipid oxidation and free radical‐mediated impairment of endothelial function was investigated. Results showed that iron‐mediated oxidative modification of the cell membrane in cultured bovine pulmonary endothelial cells (PAECs) was significantly attenuated by acteoside as measured by thiobarbituric acid‐reactive substances (TBARS). Fenton's reagent (H2O2/Fe2+) was used to generate hydroxyl radicals (*OH) and induce oxidative stress. Acteoside not only effectively minimized the loss of cell viability induced by hydroxyl radicals in cultured endothelial cells but also countered the free radical‐induced destruction of the endothelium‐dependent relaxation to acetylcholine in rat aorta. Furthermore, acteoside showed a dose‐dependent scavenging effect of 1,1‐diphenyl‐2‐picryl‐hydrazyl (DPPH) radicals and appeared to be the most efficient in comparison with the four reference compounds (α‐tocopherol, vitamin C, probucol and resveratrol). These data suggested that acteoside protects the cell from oxidative stress and that scavenging of free radicals could be a key mechanism contributing to the cytoprotective effect of acteoside.

The protective effect of acteoside against membrane lipid oxidation and free radical-mediated impairment of endothelial function was investigated. Results showed that iron-mediated oxidative modification of the cell membrane in cultured bovine pulmonary endothelial cells (PAECs) was significantly attenuated by acteoside as measured by thiobarbituric acid-reactive substances (TBARS). Fenton's reagent (H2O2/Fe2+) was used to generate hydroxyl radicals (*OH) and induce oxidative stress. Acteoside not only effectively minimized the loss of cell viability induced by hydroxyl radicals in cultured endothelial cells but also countered the free radical-induced destruction of the endothelium-dependent relaxation to acetylcholine in rat aorta. Furthermore, acteoside showed a dose-dependent scavenging effect of 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radicals and appeared to be the most efficient in comparison with the four reference compounds (α-tocopherol, vitamin C, probucol and resveratrol). These data suggested that acteoside protects the cell from oxidative stress and that scavenging of free radicals could be a key mechanism contributing to the cytoprotective effect of acteoside.

ABSTRACTInhibitory effects of ethanolic extracts from 10 Chinese herbs on herpes simplex virus type 1 (HSV-1) replication were investigated. By a bioassay-guided fractionation procedure, samarangenin B (Sam B) was isolated from Limonium sinense; Sam B significantly suppressed HSV-1 multiplication in Vero cells without apparent cytotoxicity. Time-of-addition experiments suggested that the inhibitory action of Sam B on HSV-1 replication was not due to the blocking of virus adsorption. In an attempt to further localize the point in the HSV-1 replication cycle where arrest occurred, a set of key regulatory events leading to viral multiplication was examined, including viral immediate-early (α), early (β), and late (γ) gene expression and DNA replication. Results indicated that levels of glycoprotein B (gB), gC, gD, gG, and infected-cell protein 5 (ICP5) expression and gB mRNA expression in Vero cells were impeded by Sam B. Data from PCR showed that replication of HSV-1 DNA in Vero cells was arrested by Sam B. Furthermore, Sam B decreased DNA polymerase, ICP0, and ICP4 gene expression in Vero cells. Results of an electrophoretic mobility shift assay demonstrated that Sam B interrupted the formation of an α-trans-induction factor/C1/Oct-1/GARAT multiprotein complex. The mechanisms of antiviral action of Sam B seem to be mediated, at least in part, by inhibiting HSV-1 α gene expression, including expression of the ICP0 and ICP4 genes, by blocking β transcripts such as DNA polymerase mRNA, and by arresting HSV-1 DNA synthesis and structural protein expression in Vero cells. These results show that Sam B is an antiviral agent against HSV-1 replication.