Search

Insulin resistance (IR) has been proposed as a contributing factor to major depressive disorder (MDD), with previous studies reporting a positive correlation between triglyceride-glucose (TyG) a proxy indicator of IR and MDD. However, limited information is available regarding their longitudinal association. This study aimed to clarify the connection between TyG levels and depression risk, as well as explore its predictive potential. A total of 3021 participants without a prior history of depression were recruited from the China Health and Retirement Longitudinal Study and followed for seven years. Participants were categorized into tertiles based on their TyG levels. The cumulative hazard of depression was analyzed using Kaplan-Meier curves, while cox regression analyses and multivariable-adjusted restricted cubic spline (RCS) curves were employed to assess the relationship between TyG levels and depression risk. Stratified analyses across various subgroups were also conducted to confirm the robustness of the conclusions. Over the follow-up period, 1782 participants (58.9%) developed depression, with incidence rates of 30.2%, 34.0%, and 35.8% in tertiles 1, 2, and 3, respectively. After adjusting for confounding factors, each 1-unit increase in TyG was associated with a significantly higher risk of depression. RCS curve analysis revealed a compelling dose-response relationship between TyG levels and depression susceptibility. These findings indicate that elevated TyG levels are strongly associated with an increased risk of depression and could serve as a reliable biomarker for assessing depression risk. These insights provide valuable guidance for developing more effective strategies for the prevention and treatment of depressive disorders.

Background: Depression is a common mental illness that has become a major economic burden worldwide. Recently, increasing evidence has highlighted the inflammatory mechanism of depression. In order to understand the research status of this field, this study used the bibliometric analysis method to overview the research content and progress, as well as analyze the development trend and limitations., Methods: In this study, articles and reviews were included in the specific search strategy. The matched papers were exported from the Web of Science database. CiteSpace 6.3 R1 and Bibliometrix (R package) were utilized to generate bibliometric and knowledge maps., Results: A total of 25,063 articles were included in this study. The number of publications in this field has gradually increased, especially in recent years. These papers come from 156 countries, led by the United States and China mainland. The leading research institution is the University of Toronto (Canada). Brain Behavior and Immunity is the journal with the most publications and the most frequently co-cited journals. Among 91,100 authors, Maes M has the most publications and co-citations. According to the keywords burst and co-cited reference analysis, the hotspots in the field in recent years include kynurenine, c-reactive protein, neuroinflammation, and gut microbiota., Conclusion: Although abundant academic achievements have been made on the inflammatory mechanism of depression, there is still a long way to go before these research results can be applied to clinical practice. Strengthening international academic exchanges and cooperation may promote breakthroughs in this field., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Circular RNAs (circRNAs) have emerged as essential regulators in cardiovascular disease, including acute myocardial infarction (AMI). This study investigated the role of circRNA Pum1_0014 in myocardial infarction (MI) and its underlying mechanisms using an H9C2 cell model. Through Sanger sequencing, nucleic acid electrophoresis, RNase R, and transcriptional inhibition experiments, Pum1_0014 was identified as a novel circRNA. The cell localization of circRNA Pum1_0014 was detected by qPCR and fluorescence in situ hybridization, and the results revealed that circRNA Pum1_0014 is predominantly located in the cytoplasm. StarBase (URL: http://starbase.sysu.edu.cn/) and TargetScan (URL: https://www.targetscan.org/vert_80/) were used to predict circRNA Pum1_0014 targeting miRNAs and miRNA targeting mRNA, and the results identified miR-146a-5p as a potential target of Pum1_0014, which in turn targets NF2. The plasmid encoding the mutant circRNA Pum1_0014 or the 3'UTR mutant NF2 was constructed, and the interaction between Pum1_0014 and miR-146a-5p or miR-146a-5p and NF2 was detected by luciferase reporter gene assay. The results confirmed the interactions between Pum1_0014, miR-146a-5p, and NF2. In the MI cell model, upregulation of circRNA Pum1_0014 and NF2 and downregulation of miR-146a-5p were observed. Knockdown of circRNA Pum1_0014 inhibited NF2 expression and activated the VEGF/PAK1 pathway, reducing cardiomyocyte apoptosis. Conversely, inhibition of miR-146a-5p and overexpression of NF2 had opposite effects. These findings suggest that circRNA Pum1_0014 acts through the miR-146a-5p/NF2 axis to reduce cardiomyocyte apoptosis in MI via the VEGF/PAK1/NF2 pathway.

Samples of ambient volatile organic compounds （VOCs） were collected using SUMMA canisters at three Country Control Sites in Shijiazhuang during the spring of 2019, 2021, and 2022, which were detected using gas chromatography/mass spectrometry （GC/MS）. To investigate the characteristics and temporal variations of VOCs mass concentration levels, the online monitoring data of ozone （O 3 ） and PM 2.5 at the same site were also collected. Subsequently, the ozone formation potential （OFP） and secondary organic aerosol formation potential （SOAFP） were utilized to assess the chemical activity of VOCs. Additionally, the potential source areas of VOCs in spring in Shijiazhuang were further identified using the potential source contribution factor （PSCF） method and concentration weight trajectory analysis （CWT）. Hence, the major VOCs sources were evaluated with the VOCs initial mixing ratio. The results demonstrated that the averaged concentration of VOCs during the polluted period and clean period of spring in Shijiazhuang were 191.17 μg·m -3 and 122.18 μg·m -3 , respectively. Meanwhile, the OFP was 361.23 μg·m -3 during the polluted period and 266.96 μg·m -3 during the clean period, whereas the SOAFP was 1.98 μg·m -3 and 1.61 μg·m -3 , respectively. Therefore, effective control of benzene, toluene, ethylbenzene, and xylene （BTEX） is crucial for reducing PM 2.5 and O 3 pollution. Based on the results obtained from weight PSCF and CWT, the potential source areas of VOCs were further identified to be primarily located in the eastern Yuhua District, the high-tech district, and the northern Luancheng District of Shijiazhuang. These areas were influenced not only by local emissions but also by transport from neighboring regions, in which consistency between the CWT and PSCF results further supported these findings. Furthermore, the results obtained from the benzene/toluene/ethylbenzene （B/T/E） and xylene/benzene （X/B） ratios indicated that the main sources of VOCs in Shijiazhuang in spring were vehicle exhaust sources and burning sources, leading to a more serious air mass aging phenomenon. Hence, controlling vehicle emissions and implementing regional cooperative measures are the effective strategies for optimizing the air quality of Shijiazhuang.

Drought intensity and frequency have been increased as a result of global warming. Exploring the drought resistance mechanism of Robinia pseudoacacia plantations of different stand ages on the Loess Plateau is crucial for understanding the stability of forest productivity in the region. We investigated anatomical traits, hydraulic function, and non-structural carbohydrate content of the xylem, as well as their association, in R. pseudoacacia plantations of different stand ages in a semi-arid region. The results showed that the vessel diameter, total pit membrane area, pit membrane area, vesture area, and vestured overlap of young and middle-aged stands were larger than those of mature stands, and the pit density was significantly lower in mature stands. Hydraulic conductivity was significantly related to vessel diameter, pit membrane area, and vesture area. Hydraulic conductivities of branches in young, middle-aged, and mature stands were 2.30, 2.12, and 0.76 kg·m -1 ·s -1 ·MPa -1 , respectively, with embolism values of 54.5%, 53.8%, and 45.1%. Hydraulic conductivity was significantly related to soluble sugar and starch contents. The soluble sugar contents of branches in young, middle-aged and mature stands were 4.9%, 4.2%, and 3.8%, respectively. Xylem growth capacity of R. pseudoacacia in mature stand declined, resulting in the formation of small vessels with many small pits, which reduced hydraulic conductivity while maintaining hydraulic safety, resulting in a decrease of non-structural carbohydrates content. This study revealed the drought response mechanism of R. pseudoacacia plantations with different ages, providing a scientific foundation for the management and nurturing of R. pseudoacacia plantations on the Loess Plateau.

Sickle cell disease (SCD) is a single gene genetic disease, which seriously threatens the life span and quality of patients. On the basis of the pathogenesis of SCD and the alternative therapy based on fetal hemoglobin F (HbF), the research progress of transcription factors involved in the regulation of HbF gene expression, such as BCL11A, ZBTB7A, KLF-1, c-MYB and SOX6, as well as the application of CRISPR / Cas9, TALEN, zinc finger nuclease and other gene editing technologies in this field has been made, providing a solid theoretical basis for the exploration of new treatment schemes for β- like hemoglobin diseases, such as sickle cell disease and β- thalassemia.

The effect of hydraulic retention time (HRT) on denitrifying phosphorus and nitrogen removal in a modified two sludge A 2 /O-BAF system was studied. The influent COD, NH 4 + -N, and TP were 189.6, 60.4, and 5.1 mg·L -1 , respectively. When HRT was 9, 8, 7, and 6 h, the average effluent COD was less than 42 mg·L -1 . The average effluent NH 4 + -N levels were 2.4, 2.8, 3.3, and 6.5 mg·L -1 , respectively. The average effluent TP values were 0.3, 0.4, 0.7, and 0.8 mg·L -1 , respectively. The ratio of the denitrifying phosphorus accumulation organisms (DPAOs/PAOs) in the system of anoxic zone was reduced from 76.8% to 48.8%. When HRT was 8 h, the ratio of denitrifying phosphorus to nitrogen (ΔPO 4 3- /ΔNO 3 - -N) was increased by 37.5% by a mathematical statistics method. The ΔPO 4 3- /ΔNO 3 - -N in the anoxic zone was 1.24 (the theoretical value is 1.41). At this time, the effect of denitrifying phosphorus to nitrogen was the best. The SVI value was lower than 100 mL·g -1 throughout the experiment, and the MLVSS/MLSS gradually decreased from 0.74 to 0.63, indicating that the sludge activity was reduced.

The increase of ground-level ozone concentration significantly reduces rice yield, but its effect on grain quality in association with the positions on a panicle was largely unknown. The effects of ozone stress on amylose content and RVA profile of rice grains located at different positions of panicles were studied by using a sunlit gas fumigation platform. Eight varieties representing different types of rice were fumigated under ambient (9 nL·L -1 ) or elevated ozone (100 nL·L -1 ) concentrations from transplanting until maturity. The results showed that elevated ozone treatment significantly reduced amylose content, maximum viscosity, hot viscosity, breakdown and cold viscosity by 5.9%, 7.6%, 5.9%, 11.6%, 2.9%, respectively, but increased the setback and gelatinization temperature by 24.9% and 1.0%. There were significant differences among varieties for amylose content and all parameters in RVA profile. The grains located at different positions on a panicle differed in amylose content, maximum viscosity, hot viscosity, breakdown and cold viscosity. The superior grains located at the upper part of a panicle had the highest value and the inferior grains located at the lower part of a panicle had the lowest value. However, the setback in RVA profile showed a different trend, with the superior grains having the lowest setback but inferior grains having the highest setback. In most cases, there were significant interactive effects of ozone by year or ozone by variety on amylose content and RVA profile. No significant ozone by grain position interaction on RVA profile was found, although the responses of superior grains to ozone stress was slightly smaller than those of inferior grains or grains located at the middle part of a panicle. The results demonstrated that ozone fumigation of 100 nL·L -1 during rice growing season deteriorated rice quality, with the magnitude of deterioration varying with growth seasons and varieties and little impacts of grain positions on a panicle.

The rising atmospheric CO 2 concentration affects spikelets development, grain filling process, and rice quality. However, it is unclear that whether such effects are related to grain positions on rice panicle. By using a rice FACE (Free-Air CO 2 Enrichment) platform, we grew a japoni-ca rice cultivar Wuyunjing 23, characterized with high yield and good quality, under ambient (Ambient) and elevated CO 2 concentrations (+200 μmol·mol -1 , FACE). The effects of increased CO 2 concentration on spikelet density, grain filling capacity, the appearance and eating quality of rice grains were examined and the association of such effects with grain positions on rice panicle were investigated. The results showed that CO 2 enrichment increased grain yield of Wuyunjing 23 by 18.3%. The panicle number per unit land area and filled-grain weight increased by 21.4% and 9.4%, respectively; whereas the number of spikelets per panicle and filled-grain percentage decreased by 9.0% and 2.2%, respectively. The decreased filled-grain percentage of rice grown under FACE treatment was mainly related to the increases of empty-grain percentage in all parts of rice panicle. The decrease of rice spikelets number per panicle by FACE treatment was mainly due to the substantial decrease of surviving spikelets of secondary branches in upper and middle parts of rice panicles instead of other positions. The CO 2 -induced changes of filled-grain weight and filled-grain percentage were similar among grains located at different positions on rice panicle. FACE treatment reduced the green grain rate and increased the grain length and width, with the grains at different positions on rice papnicle showing similar responses. FACE significantly increased chalky grain percentage by 59% and chalkiness degree by 55%, with the increases for both parameters following the order of primary branches＞secondary branches and upper part＞middle part＞lower part. FACE treatment slightly increased amylose content while decreased peak viscosity, hot viscosity, breakdown, final viscosity and setback, but most of these effects were nonsignificant. The gelatinization temperature of rice also reduced by 5% under FACE, and the decrease of inferior spikelets was greater than that of superior spikelets. In summary, the yield increase of Wuyunjing 23 under high CO 2 concentration was mainly related to the increases of panicle number and individual grain weight, while the panicle size was reduced. Elevated CO 2 concentration reduced green grain percentage but increased grain chalkiness, and had little effect on cooking and eating quality. The grain positions on rice panicle affected the responses of spikelets development, grain filling capacity and grain quality of rice to elevated CO 2 concentration, but the effects varied across different indices.

Transition-metal sulfides hold great promise as anode materials for sodium-ion batteries due to the high theoretical capacity and excellent redox reversibility based on multielectron conversion reactions. In this work, an elaborate composite, cobalt sulfide nanoclusters embedded in honeycomb-like sulfur-doped carbon foam (Co 9 S 8 @S-CF), is prepared via a facile sulfur-assisting calcination strategy, which tactfully induces the co-occurrence of in situ pore-forming, sulfidation, sulfur doping, and carbonization. Notably, sulfur-doped carbon foam (S-CF) possesses abundant voids, which are subject to construction of three-dimensional ionic/electronic pathways, leading to high sodium-ion accessibility and ultrafast sodium-ion/electron transportation toward Co 9 S 8 nanoclusters. When worked as an anode in sodium-ion batteries, it delivers a remarkable capacity of 373 mA h g -1 over 1000 cycles at 0.25 C, achieving superior capacity retention of 80%. Furthermore, this anode could achieve unprecedented rate capability with a reversible capacity of 180 mA h g -1 at 50 C (20 A g -1 ), which significantly precedes those reported previously.

Light and carbon dioxide (CO 2 ) are two essential components for plant photosynthesis. To understand the effects of elevated CO 2 concentration on photosynthetic characteristics of hybrid rice under different light conditions, two hybrid rice varieties (YLY900 and YY538) were grown in the field using a free-air CO 2 enrichment facility (FACE) in 2017 with two CO 2 concentration treatments (ambient CO 2 and elevated 200 μmol·mol -1 above ambient CO 2 ), the photosynthesis traits of top full expansion leaves were measured in both sunny and cloudy days at jointing and grain filling stages. Elevated CO 2 increased net photosynthetic rate (P n ) of two rice varieties. The increase in sunny days (31%) was greater than in cloudy days (21%), and the increase at jointing stage (37%) was greater than at grain filling stage (21%). There were significant interactions between CO 2 with weather, and between CO 2 with growth stage. Water use efficiency (WUE) of leaves in response to elevated CO 2 showed the similar trend as P n . Elevated CO 2 decreased stomatal conduc-tance (g s ) and transpiration rate (T r ), and the decreases in sunny days were greater than that in cloudy days. The P n , g s , T r , WUE and stomatal limit (L s ) measured in cloudy days were significantly lower than that measured in sunny days by 41%, 18%, 41%, 26% and 27%, respectively. Results from the correlation analyses showed that the P n , g s , and T r in sunny days were significantly positively correlated with the corresponding parameters in cloudy days. The results indicated that cloudy weather conditions reduced photosynthesis and its response to elevated CO 2 of two hybrids rice varieties at middle and late growth stages. Therefore, weather variation should be considered when assess rice yield potential in the future environment.

This study aimed to investigate the effect of butyl alcohol extract of Baitouweng Decoction( BAEB) on Candida albicans biofilms based on pH signal pathway. The morphology of biofilms of the pH mutants was observed by scanning electron microscope. The biofilm thickness of the pH mutants was measured by CLSM. The biofilm activity of the pH mutants was analyzed by microplate reader.The biofilm damage of the pH mutants was detected by flow cytometry. The expression of pH mutant biofilm-related genes was detected by qRT-PCR. The results showed that the deletion of PHR1 gene resulted in the defect of biofilm,but there were more substrates for PHR1 complementation. BAEB had no significant effect on the two strains. RIM101 gene deletion or complementation did not cause significant structural damage,but after BAEB treatment,the biofilms of both strains were significantly inhibited. For the biofilm thickness,PHR1 deletion or complementation caused the thickness to decrease,after BAEB treatment,the thickness of the two strains did not change significantly. However,RIM101 gene deletion or complementation had little effect on the thickness,and the thickness of the two strains became thinner after adding BAEB. For biofilm activity,PHR1 deletion or complementation and RIM101 deletion resulted in decreased activity,RIM101 complementation did not change significantly; BAEB significantly inhibited biofilm activity of PHR1 deletion,PHR1 complemetation,RIM101 deletion and RIM101 complemetation strains. For the biofilm damage,PHR1 gene deletion or complementation,RIM101 gene deletion or complementation all showed different degrees of damage; after adding BAEB,the damage rate of PHR1 deletion or complementation was not significantly different,but the damage rate of RIM101 deletion or complementation was significantly increased. Except to the up-regulation of HSP90 gene expression,ALS3,SUN41,HWP1,UME6 and PGA10 genes of PHR1 deletion,PHR1 complementation,RIM101 deletion,and RIM101 complementation strains showed a downward expression trend. In a word,this study showed that mutations in PHR1 and RIM101 genes in the pH signaling pathway could enhance the sensitivity of the strains to the antifungal drug BAEB,thus inhibiting the biofilm formation and related genes expression in C. albicans.

To explore the activity of essential oil extracted from Artemisia argyi (AAEO) in inducing the apoptosis of Candida albicans SC5314. The effect of AAEO on reactive oxygen species(ROS) and mitochondria membrane potential(MMP) of C. albicans SC5314 was detected by flow cytometry. Phosphatidylserine externalization was observed under fluorescence microscopic with Annexin-V/PI staining at the early stage of apoptosis in C. albicans. Metacaspase activity was observed under fluorescence microscopic with FITC-VAD-FMK staining at the early stage of apoptosis in C. albicans. C. albicans morphology was observed by DAPI nuclear staining and fluorescence microscopy. After intervention with 0.5 mL•L⁻¹ AAEO, apoptosis of C. albicans significantly increased, metacaspase activity increased, nuclear pyknosis and fragmentation, and intracellular ROS were significantly increased, and mitochondrial membrane potential decreased significantly. The certain concentrations of AAEO could induce the apoptosis of C. albicans., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Objective: To observe the efficacy of chemotherapy consisted of bortezomib as main druy in maintenance therapy for recurrence of newly diagnosed MM patients., Methods: The clinical data and outcome of 37 MM patients during 2008-2013 were analyzed retrospectively, the 37 MM patients were divided into 2 group: 19 cases including 13 cases of newly diagnosed MM with symptoms and 6 cases of relapsed refractory MM were enrolled in group A; 17 cases of newly diagnosed MM with symptoms were enrolled in group B. The patients of group A received maintenance therapy consisted of bortezomib plus dexamethasone (VD group), while the patient group B received maintenance therapy consisted of melphalan plus prednisone(MP group), then the therapeutic efficacy of 2 group was compared., Results: The overall response rate(ORR) in VD groupe was 84.2%(16/19), out of which CR rate reached 42%(8/19), PR rate reached 31.6%(6/19), MR rate reached 10.5%(3/19). During median follow-up for 21.8(5-51) months, death occurred, while the ORR in MP group was 52(9/17), out of which CR rate was 23.5%(4/17), PR rate reached 23.5%(4/17), MR rate reached 5.9%(1/17). Druing median follow-up for 16.4(4-39) months, the worteity reaced 64.7%(11/17). The differencr between 2 groups was significant(P<0.05). The median OS time of patients in VD group was 21.6 months, that in MP group was 17.9 months(P<0.05). The median PFS in VD group and MP group were 13.4 and 9.4 months respectively(P<0.001)., Conclusion: The ORR and CR rates of bortezomib maintenance therapy for newly diagnosed and relapsed / refractory MM patients are very high, and its toxicity can be controlled, therefore, the patients need maintenance therapy after remission.

Background: Abundant researches indicate that neuroinflammation has important roles in the pathophysiology of depression. Our previous study found that the NLRP3 inflammasome mediated stress-induced depression-like behavior in mice via regulating neuroinflammation. However, it still remains unclear that how the NLRP3 inflammasome influences related inflammatory signaling pathway to contribute to neuroinflammation in depression., Methods: We used wild-type mice and NLRP3 gene knockout mice to explore the role of NLRP3 inflammasome and related inflammatory signaling pathways in chronic unpredictable mild stress (CUMS) induced depression mouse model., Results: Both wild-type and NLRP3 knockout stress group mice gained less weight than control group mice after 4 weeks CUMS exposure. The wild-type mice subjected to 4 weeks CUMS displayed depression-like behaviors, including decreased sucrose preference and increased immobility time in the tail suspension test. The NLRP3 knockout stress group mice didn't demonstrate depression-like behaviors. The levels of interleukin-1β protein in serum and hippocampi of CUMS exposed wild-type mice were significantly higher, while the NLRP3 knockout stress group mice didn't show an elevation of interleukin-1β levels. Similarly to early researches, we found that CUMS led to promoted NLRP3 expression in hippocampi. In addition, the hippocampi in CUMS exposed wild-type mice had higher p-JNK and p-p38 protein expression, which indicated activation of the mitogen-activated protein kinases (MAPK) pathway. The knockout of NLRP3 gene inhibited CUMS-induced activation of the MAPK pathway. The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) protein complex was activated in the hippocampi of wild-type mice after CUMS exposure, while knockout of NLRP3 gene hindered its activation., Conclusions: These data further proved that the NLRP3 inflammasome mediated CUMS-induced depression-like behavior. The NLRP3 inflammasome regulated CUMS-induced MAPK pathway and NF-κB protein complex activation in depression mouse model. Further researches targeting the NLRP3 inflammasome-signaling pathway might be under a promising future in the prevention and treatment of depression., (Copyright © 2017 Elsevier B.V. All rights reserved.)

High mobility group box 1 (HMGB1) has been implicated as a key factor in several neuroinflammatory conditions. Our previous study suggested that the release of central HMGB1 acts as a late-phase mediator in lipopolysaccharide (LPS)-induced depression. Recent findings indicate that the redox state of HMGB1 is a critical determinant of its immunomodulatory properties. Here, we aimed to investigate the potential mechanisms that link the redox states of HMGB1 to depression in mice. Distinct redox forms of recombinant HMGB1 (rHMGB1) were used that included fully reduced HMGB (fr-HMGB1), which acted as a chemokine, and disulfide-HMGB1 (ds-HMGB1), which possessed cytokine activity. Fr-HMGB1 in vivo was partially oxidized into ds-HMGB1; thus, the mutant protein non-oxidizable chemokine-HMGB (nonoxid-HMGB1) was applied. Concurrent with depressive behavior induced by four-week stress exposure, the HMGB1 concentrations in the serum and cerebral cortex substantially increased. Therefore, a single dose of rHMGB1 (200ng/5μl/mice) or vehicle was administered to mice via intracerebroventricular (i.c.v.) injection. The receptor inhibitors of TLR4/RAGE/CXCR4 (TAK-242/FPS-ZM1/AMD3100) (3mg/kg) were intraperitoneally injected 30min prior to rHMGB1 treatment. Depressive-like behavior was measured 20h post i.c.v. injection. Administration of fr-HMGB1 prolonged the immobility duration in the tail suspension test (TST) and decreased sucrose preference. In addition to depressive behavior, the hippocampal TNF-α protein slightly increased. These depressive behaviors and upregulation of hippocampal TNF-α were alleviated or abrogated by pretreatment with the inhibitors AMD3100, FPS-ZM1, and TAK-242. Alternatively, nonoxid-HMGB1 failed to induce TNF-α protein or prolong the immobility duration. As expected, ds-HMGB1 administration substantially upregulated hippocampal TNF-α protein, increased the immobility time in the TST and decreased sucrose preference. Moreover, both glycyrrhizin and TAK-242 improved ds-HMGB1-induced depressive behavior. Furthermore, TAK-242 significantly blocked the upregulation of hippocampal TNF-α protein and protected hippocampal myelin basic protein from ds-HMGB1-induced reduction. These drugs had no effect on the total or central distance in the open field test. Collectively, this initial experiment demonstrates the role and receptor mechanisms of HMGB1 under different redox states on the induction of depressive-like behavior. Both ds-HMGB1 and fr-HMGB1 may induce depressive-like behavior in vivo mainly via neuroinflammatory response activation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To investigate the correlation of patients with thrombosis or prothrombotic status with hyperhomocysteinemia (HHcy), activated protein C-resistance(APCR) and gene polymorphism of coagulation factor V., Methods: Three hundred healthy voluteers were selected as controls, 223 cases of thrombosis (80 cases of cerebral infarction of CT, the MI of 82 cases of myocardial infarction, venous thrombosis of VTE 61 cases), 270 cases of patients with prothrombotic state (76 cases of pregnancy disease of PIH, 62 cases of chronic obstructive pulmonary disease (COPD), 60 cases of diabetes(DM) and 72 cases of cancer) were enrolled in this study. The plasma APCR and hyperhomocysteinemia were detected by APTT coagulation method and cycling enzyme method respectively, and restriction fragment length polymorphism(RFLP) were was used to detect the gene polymorphism of FV G1691-A, G1091-C and A1090-G in the patient and control groups., Results: APCR positive rate was 62.29% and 7.33%, and the positive hyperhomocysteinemia accounted for 68.42% and 10.00% respectively in the group of the patients with venous thrombosis and the normal control group. 3 cases of heterozygous FV gene mutations were found in the APCR-positive patients with venous thrombosis., Conclusion: HHcy possitive rate of patients with venous thrombosis is signiticantly higher than that in control, the HHcy is one of the important causes resulting in thrombosis, the patients with venous thrombosis have proved to be with APCR, and the possitive APCR may be related with the coagulation factor V gene polymorphism.

The hydrothermally synthesized layered chalcogenide, K(2x)Mn(x)Sn(3-x)S6 (x=0.5-0.95) (KMS-1), was applied to remove ciprofloxacin from aqueous solution. Kinetic data showed the removal reaction followed a pseudo-second-order kinetic model and the rate controlling step was both through external film and intraparticle diffusion. The adsorption of CIP by KMS-1 is endothermic and the maximum adsorption capacity of KMS-1 was 199.6, 230.9 and 269.5 mg/g at temperature of 10, 25 and 40°C, respectively. The heavy metal ions had great effect on the removal efficiency of CIP and the degree of inhibition followed the order: Pb(2+)>Zn(2+)>Cd(2+)>Ni(2+). The shift of Bragg peaks from XRD at various pH accompanying CIP removal and FE-SEM images confirmed that cation exchange is the major mechanism for the adsorption of CIP by KMS-1. In the pH range of 4.0-7.0, the intercalation of cationic CIP adopted a titled orientation of di-molecular CIP in KMS-1 with the titling angle of 68° and 42°, respectively. A vertical arrangement of the zwitterionic CIP adsorbed on the surface of KMS-1 was also confirmed. These results suggested that KMS-1 is an effective adsorbent to remove CIP from water., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Depression disorder is a common mental illness, of which the pathogenesis is not well understood. Studies suggest that immunity imbalance and up-regulation of pro-inflammatory cytokines may be associated with the pathogenesis of depression. High-mobility group box 1 protein (HMGB1) has gained much attention as an important player in innate immune responses and an modulating factor in several inflammatory diseases. Here we sought to explore the role of HMGB1 in the development of depression. Depression model was established with low dose of lipopolysaccharide (LPS) administration. Depressive behavior was reflected with increased immobility time in tail suspension test. Accompanying with depressive-like behavior, translocation of HMGB1 from nuclei to cytoplasm was observed by immunofluorescence assays. Meanwhile, no significant necrosis was observed evaluated by hematoxylin-eosin staining. These data indicated that HMGB1 was released actively in the central nervous system. In addition, treating the mice with human recombinant HMGB1 (rHMGB1) could induce the development of depressive-like behavior. Blockage of HMGB1 with GZA abrogated the depressive-like behavior induced by LPS or rHMGB1. These results implicated that HMGB1 was involved in LPS-induced depressive-like behavior., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In order to investigate the effects of ozone stress on photosynthesis, dry matter production, non-structural carbohydrate and yield formation of rice, a free air ozone concentration enrichment (FACE) experiment was conducted. A super hybrid rice cultivar II-you 084 with 3 spacing levels, low plant density (LD, 16 hills per m2), medium (MD, 24 hills per m2) and high plant density (HD, 32 hills per m2), was grown in the field at current and elevated ozone concentrations (current × 1.5). The results were as follows: Elevated ozone significantly reduced leaf SPAD value of UI-you 084 by 6%, 11% and 13%, at 63, 77, and 86 days after transplanting, respectively. The declines in leaf net photosynthetic rate, stomatal conductance and transpiration rate at filling stage increased significantly on ozone stress over time. Ozone stress decreased dry matter production of rice by 46% from heading stage to plant maturity, thus reduced biomass yield by 25%. Elevated ozone decreased the concentration and accumulation of soluble carbohydrate and starch in stem of II-you 084 at jointing, heading and plant maturity, but significantly increased the dry matter transportation rate. No significant interaction was observed between ozone and planting density for photosynthesis, dry matter production and non-structural carbohydrate of rice. The above results indicated that elevated ozone reduced photosynthesis and growth of rice II-you 084 at late growth stage, which had no relationship with planting density.

Depression is often preceded by exposure to stressful life events. Chronic stress causes perturbations in the immune system, and up-regulates production of proinflammatory cytokines, which has been proposed to be associated with the pathogenesis of clinical depression. However, the potential mechanisms by which stress-induced proinflammatory cytokines lead to the development of depression are not well understood. Here, we sought to screen the main proinflammatory cytokines and the potential mechanisms linking inflammation to depression-like behavior during unpredictable, chronic, mild stress (UCMS), in vivo. Mice were allocated into four groups in each separate experiment: saline-control, saline-UCMS, drug-control and drug-UCMS. Development of depression-like behavior was reflected as a reduction in sucrose preference, and increased immobility in both the forced swim and tail suspension tests. The following drugs were administered intraperitoneally: the pan-anti-inflammatory tetracycline derivative, minocycline (30 mg/kg, daily), the tumor necrosis factor (TNF)α monoclonal antibody, infliximab (10 mg/kg, twice weekly), and the indoleamine 2, 3-dioxygenase (IDO) inhibitor, 1-methyltryptophan (1-MT, 10 mg/mouse, daily). Plasma TNFα, IL-1β and IL-18 increased significantly after the four-week UCMS exposure. Pretreatment of mice with minocycline completely blocked any upregulation. Concurrent with development of depression-like behaviors, the concentration of TNFα in plasma and the cerebral cortex increased remarkably. The tryptophan-degrading enzyme IDO was up-regulated in the cortex following UCMS exposure. Treatment of mice with minocycline, infliximab or 1-MT prevented the development of depression-like behaviors. Furthermore, blockade of TNFα inhibited expression of IDO and protected cortical neurons from UCMS-induced damage. These results suggest that TNFα plays a critical role in mediating UCMS-induced depression through up-regulation of IDO and subsequent damage of cortical neurons.

Aims: The NLRP3 inflammasome is a cytoplasmic multiprotein complex of the innate immune system that regulates the cleavage of interleukin-1β and interleukin-18 precursors. It can detect a wide range of danger signals and trigger a series of immune-inflammatory reactions. There were plenty of studies indicating that activation of the immune system played pivotal roles in depression. However, the underlying mechanisms of immune-depression interactions remained elusive and there was no report about the involvement of inflammasome activation in depression., Methods: We established an acute depression mouse model with lipopolysaccharide to explore the involvement of inflammasome activation in depression., Results: The lipopolysaccharide-treated mice displayed depressive-like behaviors and pro-inflammatory cytokine interleukin-1β protein and mRNA levels significantly increased. The NLRP3 inflammasome mRNA expression level also significantly elevated in depressed mice brain. Pretreatment with the NLRP3 inflammasome inhibitor Ac-YVAD-CMK significantly abrogated the depressive-like behaviors induced by lipopolysaccharide., Conclusion: These data suggest for the first time that the NLRP3 inflammasome is involved in lipopolysaccharide-induced mice depressive-like behaviors. The NLRP3 inflammasome may be a central mediator between immune activation and depression, which raises the possibility that it may be a more specific target for the depression treatments in the near future., (© 2013 John Wiley & Sons Ltd.)

Quantitative characterization of skin collagen on photo-thermal response and its regeneration process is an important but difficult task. In this study, morphology and spectrum characteristics of collagen during photo-thermal response and its light-induced remodeling process were obtained by second-harmonic generation microscope in vivo. The texture feature of collagen orientation index and fractal dimension was extracted by image processing. The aim of this study is to detect the information hidden in skin texture during the process of photo-thermal response and its regeneration. The quantitative relations between injured collagen and texture feature were established for further analysis of the injured characteristics. Our results show that it is feasible to determine the main impacts of phototherapy on the skin. It is important to understand the process of collagen remodeling after photo-thermal injuries from texture feature.

Purpose: To explore the relations between Streptococcus sobrinus (S. Sobrinus) and rampant caries in children., Methods: Based on previous investigation result for rampant caries in Zhengzhou city, 66 children aged 3-5 years were selected by random sampling, and divided into 3 groups of rampant caries, high dental caries and no caries, 22 cases in each group. The final identification of S. mutans and S. sobrinus were performed after using culture medium TYCSB to operate preliminary screening of Streptococcus mutans (S. Mutans) and S. Sobrinus with polymerase chain reaction(PCR) combined with physiological and biochemical identification. SPSS10.0 software package was used to compare the detection rate and mean values of S.mutans and S.sobrinus in the experimental group and the control group., Results: It was found that single S. sobrinus without S. mutans was not detected from dental plaque in each group. The detection rate of S. mutans in group of rampant caries was higher than in group of high dental caries, but there was no significant difference (P>0.05). The difference of detection rate of S. sobrinus between the two groups and the detection rate of S. mutans between group of rampant caries and group without caries was significant(P<0.05). The difference of the detection rate of S. sobrinus between group of rampant caries and group without caries was also significant(P<0.01). The incidence of rampant caries, DMFT, DMFS, smooth-surface caries among the sample with both of S. sobrinus and S. mutans detected and the sample only with S. mutans and the sample without S. sobrinus and S. mutans were significantly different (P<0.01)., Conclusions: The main pathogenic bacteria of rampant caries in children are S. mutans and S. sobrinus. The incidence of rampant caries was related to S. sobrinus, which had synergic effect on the occurrence and development of rampant caries in children.

Depression is a very common mental health problem in our modern society. Stress is involved in the provocation of depression. The pathogenesis of depressive disorder is still not well known. The development of neuroendocrine immunology opens a new sight for clarification of mechanism underlying stress-induced depression. Chronic stress activates peripheral and central immune systems accompanied with the release of inflammatory mediators, including cytokines. Activated immune system mediates the process of depression through the interaction with neuron system and neuroendocrine system, including regulating the monoamine neurotransmitter system in synthesis, metabolism and reuptake, inducing the overactivation of hypothalamus-pituitary-adrenal (HPA) axis and its negative feedback regulation, and reducing neurogenesis. This present paper reviews the cytokines mechanisms underlying stress-induced depression.

Background: Bisphosphonates (BPs) have been reported to reduce local recurrence in giant cell tumor (GCT) of bone because of their osteoclast-suppressing effect; however, the optimal mode of delivery and the dose and duration of treatment of BPs remain to be established. To address these issues, it is first necessary to clarify the manner of action of BPs on osteoclasts. We herein evaluated the osteoclast-suppressing effect of sodium ibandronate in vitro., Methods: Mouse osteoclasts (OCLs) were generated in vitro using mouse bone marrow mononuclear cells. First, various concentrations of sodium ibandronate and equal amounts of phosphate-buffered saline were added to cell culture media. The number of multinucleated cells (over three nuclei) was recorded in each group, OCL formation was compared, and the most effective concentration of sodium ibandronate was determined. Then, high concentrations of sodium ibandronate were added to the experimental cell culture media; no ibandronate was given in the control group. Comparisons were made between the two groups in terms of OCL adhesion, migration, and bone resorption., Results: OCL formation was suppressed by sodium ibandronate in vitro; the most pronounced effect was observed at the concentration of 10(-5) mol/L. OCL migration and bone resorption were significantly suppressed at this concentration, though there was no effect on OCL adhesion., Conclusions: Sodium ibandronate was effective in suppressing OCLs and decreasing resorption in GCT. The strong anti-OCL effectiveness at a high concentration in vitro indicates a topical mode of application.

Objective: To observe the expression of vascular smooth muscle cells calcium channel α1C subunit (LTCCα1C) in rats exposed in low temperature., Methods: Cold-induced hypertension was established and blood pressure was measured every two weeks. The mRNA expression of L type calcium channel α1C was determined by RT-PCR., Results: The blood pressure of the rats exposed to cold environment increased. The blood pressure of experimental groups [(102.8 ± 2.25) mm Hg] began to increase from the first two weeks, compared with the control group [(89.2 ± 3.73) mm Hg], there were significant difference (P < 0.05). The blood pressure of experimental groups were (114.5 ± 4.21), (121.9 ± 3.03) mm Hg respectively at 4, 6 weeks. Compared with the control group, the expression of LTCCα1C mRNA of the cold exposure group increased significantly (P < 0.01). There was a significant correlation between the expression of LTCCα1C mRNA and the blood pressure of the rats (r = 0.86, P < 0.01)., Conclusion: Repeated cold exposure can establish cold-induced hypertension, and the level of vascular smooth muscle cells LTCCα1C expression increase.

Objective: To compare the effects of cartilage-perichondrium palisade complex and cartilage-perichondrium horseshoe complex in tympanoplasty for large tympanic membrane perforation., Methods: Nineteen patients (19 ears) undergoing tympanoplasty with cartilage-perichondrium palisade complex and 20 patients (20 ears) with cartilage-perichondrium horseshoe complex were compared for postoperative hearing and closure rate of tympanic membrane perforation., Results: The closure rates of the tympanic membrane were all 100% in both groups 3 months after the operation, while tympanoplasty with cartilage- perichondrium horseshoe complex resulted in significantly greater improvement of the postoperative air-bone gap in speech frequency., Conclusion: Both of the two auricular cartilage-perichondrium complexes produced good effects for repair large tympanic membrane perforation, but cartilage-perichondrium horseshoe complex can achieve better results in speech frequency.

Objective: To observe the effect of hydroxyethyl starch 130/0.4 (voluven) on P38 mitogen-activated protein kinases (MAPK) signal transduction pathway, with the aim of investigating the mechanism of its protective effect on acute lung injury (ALI) due to infection., Methods: Thirty male Sprague-Dawley (SD) rats were randomly divided into control group, lipopolysaccharide (LPS 10 mg/kg) group, voluven groups (LPS 10 mg/kg, and hydroxyethyl starch 130/0.4 15 ml/kg or 30 ml/kg) and alone voluven group (hydroxyethyl starch 130/0.4 30 ml/kg), with 6 rats in each group. Rats were sacrificed at 6 hours, the lungs were harvested for observation of pathological changes. The expression of p-P38, P38, p-P44/42 and P44/42 were detected with Western blotting. Activating protein-1 (AP-1) activation was measured with electrophoretic mobility shift assay (EMSA)., Results: Compared with control, p-P38, p-P44/42 and AP-1 were significantly higher in LPS group (P<0.05 or P<0.01). The expressions of p-P38 and AP-1 activation were significantly reduced in both voluven groups (all P<0.05). But there was no statistically significant difference between voluven 15 ml/kg and 30 ml/kg groups (all P>0.05)., Conclusion: Hydroxyethyl starch 130/0.4 can inhibit LPS-induced ALI by depressing expression of p-P38 and AP-1 activation in lung.

To investigate the effects of high ozone concentration on spikelet formation of hybrid rice cultivars, an experiment using a unique free air ozone concentration enrichment (ozone-FACE) system was conducted in 2007. Two hybrid rice cultivars, Shanyou 63 (SY63) and Liangyoupeijiu (LYPJ), were grown at ambient and elevated (target at 50% above ambient) ozone concentration. The results showed that compared with ambient ozone concentration, elevated ozone reduced the spikelet number per panicle by 28 and 34 (relative decrease of 15% and 13%) for SY63 and LYPJ, respectively. This reduction in spikelet number per panicle was mainly contributed to the significant decrease in spikelet number on secondary branches (SB), while only minor response was detected for the spikelet number on primary branches (PB), resulting in an increase in percentage of primary branch spikelets and a decrease in percentage of secondary branch spikelets under ozone exposure. In terms of spikelet formation, the large ozone-induced reduction in spikelet number per panicle of the two hybrid cultivars was entirely due to the suppression of spikelet differentiation per panicle (especially that on SB), while the degenerated spikelets per panicle decreased rather than increased under ozone exposure. It was suggested that corresponding measures should be adopted to mitigate the detrimental effects of ozone on the spikelet differentiation to minimize yield loss under increasing surface ozone concentration.

Ozone (O3) is recognized as one of the most important air pollutants. At present, the worldwide average tropospheric O3 concentration has been increased from an estimated pre-industrial level of 38 nl L(-1) (25-45 nl L(-1), 8-h summer seasonal average) to approximately 50 nl L(-1) in 2000, and to 80 nl L(-1) by 2100 based on most pessimistic projections. Oryza sativa L. (rice) is the most important grain crop in the world, and thus, to correctly evaluate how the elevated near-surface layer O3 concentration will affect the growth and development of rice is of great significance. This paper reviewed the chamber (including closed and open top chamber)-based studies about the effects of atmospheric ozone enrichment on the rice visible injury symptoms, photosynthesis, water relationship, phenology, dry matter production and allocation, leaf membrane protective system, and grain yield and its components. Further research directions in this field were discussed.

Background: The pathogenesis of hepatic fibrosis and cirrhosis is still not fully understood. The extracellular signal-regulated kinase (ERK) pathway is involved in the regulation of cell proliferation and differentiation. The aim of this study was to investigate the effects of PD98059, a specific inhibitor of ERK, on the cell cycle, cell proliferation, secretion of type I collagen and expression of cyclin D1 mRNA, CDK4 mRNA and transforming growth factor-beta1 (TGF-beta1) mRNA in rat hepatic stellate cells (HSCs) stimulated by acetaldehyde., Methods: Rat HSCs stimulated by acetaldehyde were incubated with PD98059 at different concentrations. The cell cycle was analysed by flow cytometry. Cell proliferation was assessed by the methyl thiazolyl tetrazolium colorimetric assay. The mRNA expression of cyclin D1, CDK4 and TGF-beta1 was examined using the reverse transcriptase-polymerase chain reaction. Type I collagen in the culture medium was detected by enzyme-linked immunosorbent assay., Results: 20, 50 and 100 micromol/L PD98059 significantly inhibited the proliferation and provoked a G0/G1-phase arrest of acetaldehyde-induced HSCs in a dose-dependent manner. The secretion of type I collagen and the expression of cyclin D1, CDK4 and TGF-beta1 mRNA in acetaldehyde-induced HSCs were markedly inhibited by 50 and 100 micromol/L PD98059, respectively., Conclusions: The ERK pathway regulates the cell proliferation, secretion of type I collagen and the expression of TGF-beta1 mRNA in rat HSCs stimulated by acetaldehyde, which is likely related to its regulative effect on the cell cycle.

Objective: To investigate the effects of PD98059 on the cell cycle, cell proliferation, the secretion of type I collagen and expression of transforming growth factor-beta-1 mRNA in rat hepatic stellate cells stimulated by acetaldehyde., Methods: Rat hepatic stellate cells stimulated by acetaldehyde were incubated with different concentrations of PD98059. The cell cycle was analyzed by flow cytometry. Cell proliferation was assessed by methyl thiazolyl tetrazolium colorimetric assay. The mRNA expression of transforming growth factor-beta-1 was examined by reverse transcriptase polymerase chain reaction. Type I collagen of the culture medium was detected by enzyme-linked immunoadsorbent assay., Results: Twenty, 50 and 100 micromol/L PD98059 could significantly inhibit the proliferation and provoke a G0/G1-phase arrest of hepatic stellate cells stimulated by acetaldehyde in a dose-dependent manner. The secretion of type I collagen and transforming growth factor-beta-1 mRNA expression of acetaldehyde-induced hepatic stellate cells were markedly inhibited by 50 and 100 micromol/L PD98059, respectively., Conclusion: Extracellular signal-regulated kinase signal transduction pathway could regulate cell proliferation, the secretion of type I collagen and transforming growth factor-beta-1 mRNA expression of rat hepatic stellate cells stimulated by acetaldehyde. This is most likely related to its regulative effect on the cell cycle.

Objective: To observe the clinical efficacy of Quyu Jiedu Recipe (, QJR) in treating endometriosis (EM), and to explore the levels of vascular endothelial growth factor (VEGF) and cell proliferative nucleoprotein antigen (Ki-67), their changes before and after treatment and the clinical significance in the trial., Methods: Fifty patients of EM were randomly assigned to two groups. The 26 patients in the QJR group were treated with QJR, and the 24 patients in the gestrinone (GT) group with gestrinone. Besides, a normal control group with 20 healthy women was set up. The therapeutic effects in the two treated groups were compared. Expressions of VEGF and Ki-67 in eutopic endometrium of all subjects (with both patients and healthy women at the median secretive phase) were determined with immunohistochemical stain before treatment, and the determination in the two treated groups was repeated after 3-month treatment in the same phase., Results: Before treatment, the VEGF and Ki-67 expression positive rates and their mean optic density (MOD) were higher in patients than in healthy women (P<0.05). After treatment, the positive rate and MOD of VEGF expression lowered significantly than before treatment (P<0.05), but those of Ki-67 changed insignificantly, and comparison between the two treated groups showed no significant difference (P>0.05)., Conclusion: QJR could markedly improve the symptoms of menorrhagia and menstrual disorder, and its mechanism might be related with the lowering of eutopic endometrial VEGF expression. VEGF and Ki-67 show a high expression in eutopic endometrium of patients with EM.

Objective: To observe the mechanism of Quyujiedu (QYJD, a method for removing stasis and detoxicating) in treating endometriosis of stasis-toxic syndrome type., Methods: Clinical study: Sixty patients were randomly divided into two groups, the treated group treated with QYJD and the control group treated with Danazol. The changes of clinical symptoms, physical signs, pregnancy rate, as well as levels of interleukin-1 (IL-1), interleukin-6 (IL-6) and endometrial antibody (EMAb) in them before and after treatment were observed. Experimental study: Sixty rats were established into endometriosis model, and randomly divided into the QYJD treated group, the Danazol treated group for positive control and the untreated group for negative control to observe the expression of Bax., Results: Clinical study showed that in the treated group and the control group, after treatment, dysmenorrhea score were 2.40 +/- 1.85 and 3.47 +/- 2.03, the menoxenia score 1.67 +/- 2.04 and 3.73 +/- 1.72 (P < 0.05), and the pregnancy rate 63.2% and 23.5% respectively, the difference between them was significant (all P < 0.05). Both of the two treatments can rectify immunity, reduce levels of IL-1 and IL-6, and lower the positive rate of EMAb. Experimental study showed that QYJD could improve the expression of Bax in ectopic endometrium, but could not affect the on-side expression of Bax in endometrium and muscle tissue., Conclusion: QYJD is effective in improving the stasis-toxic syndrome of endometriosis, its mechanism related with the regulation of the immune condition and the promotion of cell apoptosis in ectopic endometrium, indicating that QYJD is an effective remedy for endometriosis of stasis-toxic syndrome type.

The common disease asthma is characterized by the obstruction, inflammation and increased sensitivity of the airways. Glucocorticoids (GCs) are one of the most potent anti-inflammatory agents available for treating allergic disease. In this study, we report that the GC budesonide (BUD) can rapidly inhibit the histamine-induced contractions of airway smooth muscle in a process mediated by non-genomic mechanisms. The tracheas of albino Hartley guinea pigs were used. We measured the effects of BUD on the increased isometric tension of trachea segment rings and the shrinking of single airway smooth muscle cells (ASMCs) induced by histamine. With the application of each reagent, the changes in the isometric tension of the segment rings upon maximum contraction and at four time points were recorded. We found that BUD significantly suppressed the increase in isometric tension induced by histamine in guinea pigs within 15 min. We also observed that BUD can reduce the histamine-induced shrinking of single ASMCs in an even shorter time. Mifepristone (RU486) and actidione did not depress the inhibitory effect of BUD. The results preclude action via genomic-mediated responses that usually take several hours to occur. We conclude therefore that GCs have a rapid non-genomic inhibitory effect on guinea pig airway smooth muscle contractions, and provide a new way to investigate this non-genomic mechanism. Further study can provide theoretical evidence for the clinical application of GCs in asthma and other allergic diseases.

It has been demonstrated that all steroids can exert their actions by rapid non-genomic effects. Different steroids have different non-genomic mechanism. And there always occurs some new mechanism after some time. Now we review the non-genomic mechanism and significance of steroids.

Traditionally, steroid hormone effects have been described as a result of the modulation of nuclear transcription, thus triggering genomic events that are responsible for physiological effects. Despite early observations of rapid steroid effects that were incompatible with this theory, nongenomic steroid effects have been widely recognized only recently. However, the nongenomic effect of glucocorticoid (GC) on anti-inflammation and immunosuppression has not been reported. Macrophages play important roles in inflammation and the immune response. The present experiment selected macrophages as experimental cells to explore the nongenomic effects and possible mechanisms of GCs on phagocytosis and superoxide anion production. Phagocytosis by macrophages was detected by the neutral red uptake assay. The superoxide anions were measured by cytochrome C reduction assay. It was found that both 10(-4) and 10(-5) mol/L corticosterone (CORT) rapidly inhibited uptake of neutral red by macrophages in less than 30 min, and the inhibition by the former was stronger than that of the latter. CORT (10(-4) to 10(-10) mol/L) rapidly inhibited superoxide anion production by macrophages in less than 30 min. The above-mentioned effects were insensitive to the GC-receptor antagonist mifepristone (RU486) and the translation inhibitor actidione. CORT coupled to bovine serum albumin (BSA-CORT) was able to mimic the rapid inhibitory effects of CORT. The results indicated that CORT could rapidly inhibit phagocytosis and superoxide anion production by mouse peritoneal macrophages in vitro in less than 30 min by a rapid, nongenomic mechanism, which contributes to the anti-inflammatory and immunosuppressive actions of GCs. These data shed a new light on the clinical application of GCs.

We have reported that there are distinct domains in Interferon-alpha (IFNalpha) molecule mediating immune and opioid-like effects respectively. And the opioid effect of IFNalpha is mediated by mu opioid receptor. We report here the structural basis of fever induced by recombinant human IFNalpha. Two kinds of IFNalpha mutants were obtained and used to investigate the structural basis of fever of IFNalpha, which are 129Ser-IFNalpha and 38Leu-IFNalpha. The antiviral activity of 129Ser-IFNalpha almost disappeared, but there still retained the strong analgesic activity. The antiviral activity of 38Leu-IFNalpha remained, but the analgesic activity disappeared completely. It showed that IFNalpha and 129Ser-IFNalpha decreased cAMP production, induced the fever, and stimulated PGE2 to release from the hypothalamus slices, which could be blocked by naloxone, but 38Leu-IFNalpha failed. It is the first demonstration that fever induced by IFNalpha is mediated by opioid domain of IFNalpha interacting with opioid receptor. It is inferred that high-activity and low side-effect IFNalpha or other cytokines could be obtained after being changed the motifs in the tertiary structure.

Objective: It has been demonstrated that there are structural and functional similarities between interferon-alpha (INF-alpha) and endorphins. We have reported that there are distinct domains in the IFN-alpha molecule that mediate immune and analgesic effects, respectively, and that the opioid-like analgesic effect of IFN-alpha is mediated by the mu opioid receptor, thus inferring that the analgesic domain of IFN-alpha consists of Tyr(122) and the residues around Tyr(122) in the tertiary structure. The aim of this work was to further explore the molecular basis for the analgesic domain of IFN-alpha., Methods: By using site-directed mutagenesis, the structure of IFN-alpha was changed and a mutant of IFN-alpha was obtained. Then, the antiviral activity and opioid-like analgesic activity of IFN-alpha were measured., Results: When the Pro(39) residue of IFN-alpha, which is located close to the Tyr(122) residue in the tertiary structure, was mutated to Gly, the analgesic activity of this mutant was lost completely, but the antiviral activity of IFN-alpha was maintained compared with wild-type IFN-alpha., Conclusions: Combining the sequence of the endomorphin, it is suggested that the Pro(39) residue is one of the constituents of the analgesic domain of IFN-alpha and contributes to IFN-alpha binding to the mu opioid receptor., (Copyright 2002 S. Karger AG, Basel)