Association of Fokl polymorphism of the VDR gene with systemic lupus erythematosus in an adolescent population of the Colombian Caribbean

Introduction: Vitamin D and vitamin D receptor (VDR) polymorphisms are associated with autoimmune diseases including systemic lupus erythematosus (SLE). The aim of this study is to assess the genetic association between VDR polymorphisms: TaqI, ApaI, Bsml and FokI and SLE with serum levels of Vitamin D in the Colombian Caribbean population. Method: Case and control study. One hundred and thirty-three patients with SLE and 100 healthy individuals were included. VDR polymorphism were genotyped by RT-PCR and Taqman® probes. Allelic, genotypic and haplotype associations were estimated. Serum vitamin D concentrations were quantified by Elisa. Values of 30 to 100ng/ml were established as a normal reference range. P values <.05 were considered statistically significant. Results: A high prevalence of SLE was observed in women (94%) and was associated with a higher risk of SLE [OR: 10.8; 95% CI: 4.7-24.6] (p<.05). Moreover, higher risk of SLE was observed in individuals with FokI VDR [rs2228570] [OR: 1.58; 95% CI: 1.05-2.36] in allelic models. The ACCA Haplotype of TaqI/ApaI/Bsml/FokI polymorphisms was associated with higher risk of SLE [OR = 2.28, 95% CI = 1.12-4.66, psim <.01]. Vitamin D deficiency was evidenced in 11.3% of the patients. Conclusion: In this study, the VDR rs2228570 polymorphism and ACCA haplotype were associated with higher SLE risk in an adolescent population.

Introducción: La vitamina D y los polimorfismos en el receptor de vitamina D (VDR) se asocian con enfermedades autoinmunes, incluido el lupus eritematoso sistémico (LES). El objetivo de este estudio es analizar la asociación genética entre los polimorfismos de VDR (Taql, Apal, Bsml y Fokl) y la susceptibilidad al LES, así como su relación con los niveles séricos de vitamina D en población del Caribe colombiano. Metodología: Estudio de casos y controles. Se incluyeron 133 pacientes adultos con diagnóstico de LES y 100 individuos sanos. Los polimorfismos VDR fueron genotipados por RT-PCR y sondas Taqman®. Se estimaron asociaciones alélicas, genotípicas y haplotípicas. Las concentraciones séricas de vitamina D fueron cuantificadas por Elisa. Se establecieron valores de 30 a 100ng/ml como rango normal de referencia. Valores p<0,05 fueron considerados estadísticamente significativos. Resultados: Se observó una alta prevalencia de LES en pacientes femeninas (94%) y se asoció a mayor riesgo de LES (OR: 10,8; IC95%: 4,7-24,6; p < 0,05). Se evidenció mayor riesgo de LES en individuos con polimorfismo Fokl del gen VDR [rs2228570] (OR: 1,58; IC95%: 1,05-2,36) en modelos alélicos. El haplotipo ACCA de los polimorfismos Taql, Apal, Bsml y Fokl se asoció a mayor riesgo de LES (OR: 2,28, IC95%: 1,12-4,66; psim<0,01). Se evidenció deficiencia de vitamina D en el 11,3% de los pacientes. Conclusión: En este estudio, el polimorfismo VDR rs2228570 y el haplotipo ACCA se asociaron a mayor riesgo de LES en población adolescente.

Association between vitamin D deficiency and disease activity in Paraguayan patients with systemic lupus erythematosus / Asociación entre la deficiencia de vitamina D y la actividad de la enfermedad en pacientes paraguayos con lupus eritematoso sistémico

ABSTRACT Objective: To identify the association between vitamin D (VD) concentrations and the activity of systemic lupus erythematosus (SLE) and determine a supplementation dose that allows patients to maintain adequate levels of VD. Methods: Longitudinal, observational study. Serum levels of 25-hydroxy-VD were measured in 100 Paraguayan SLE patients from the Hospital de Clínicas between 2016 and 2018. To analyze the response to different doses of VD supplementation, 50 patients received 1000IU/day and the other 50 patients received 2000IU. SLE disease activity measured by SELENA-SLEDAIwas scored before and after supplementation. Results: The mean age was 27.5 ±9.8 years, 88.9% of patients presented mild disease activ ity and 11.1% presented moderate to severe activity. The mean VD concentration was 30.8 ± 11.8 ng/mL. A total of 34% of patients presented VD insufficiency and 13% VD defi ciency. There was an inverse relationship between VD concentrations and SLE disease activity (p = 0.03). Increasing levels of serum VD are associated with supplementation of 2000 IU/day (p = 0.0224). Conclusion: SLE activity was associated with low levels of VD. In our cohort, SLE patients required a supplementation dose equal to or greater than 2000 IU/day to increase their serum VD.

R E S U M E N Objetivo: Identificar la asociación entre las concentraciones de vitamina D (VD) y la actividad del lupus eritematoso sistémico (LES), además de encontrar una dosis de suplementación que les permita a los pacientes mantener niveles adecuados de VD. Métodos: Estudio observacional longitudinal. Se midieron los niveles séricos de 25-hidroxi-VD en 100 pacientes paraguayos con LES, del Hospital de Clínicas, entre los años 2016 y 2018. Para analizar la respuesta a diferentes dosis de suplementación con VD, 50 pacientes recibieron 1.000 UI/día y los otros 50 pacientes recibieron 2.000 UI/día. La actividad de la enfermedad del LES medida por SELENA-SLEDAI se puntuó antes y después de la suplementación. Resultados: La media de edad fue de 27,5 ± 9,8 años, el 88,9% de los pacientes presentó actividad leve de la enfermedad y el 11,1% presentó actividad moderada a severa. La concentración media de VD fue de 30,8 ± 11,8 ng/ml. El 34% de los pacientes presentó insuficiencia de VD y el 13%, deficiencia de VD. Hubo una relación inversa entre las concentraciones de VD y la actividad de la enfermedad del LES (p = 0,03). Los niveles crecientes de VD en suero se asocian con una suplementación de 2.000 UI/día (p = 0,0224). Conclusión: La actividad del LES se asoció con niveles bajos de VD. En nuestra cohorte, los pacientes con LES requirieron una dosis de suplementación igual o superior a 2.000 UI/día para aumentar su VD sérica.

Schisandrin B Inhibits NLRP3 Inflammasome Pathway and Attenuates Early Brain Injury in Rats of Subarachnoid Hemorrhage / 中国结合医学杂志

OBJECTIVE@#To determine whether Schisandrin B (Sch B) attenuates early brain injury (EBI) in rats with subarachnoid hemorrhage (SAH).@*METHODS@#Sprague-Dawley rats were divided into sham (sham operation), SAH, SAH+vehicle, and SAH+Sch B groups using a random number table. Rats underwent SAH by endovascular perforation and received Sch B (100 mg/kg) or normal saline after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, Evan's blue extravasation, and terminal transferase-mediated dUTP nick end-labeling (TUNEL) staining were carried out 24 h after SAH. Immunofluorescent staining was performed to detect the expressions of ionized calcium binding adapter molecule 1 (Iba-1) and myeloperoxidase (MPO) in the rat brain, while the expressions of B-cell lymphoma 2 (Bcl-2), Bax, Caspase-3, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated specklike protein containing the caspase-1 activator domain (ASC), Caspase-1, interleukin (IL)-1β, and IL-18 in the rat brains were detected by Western blot.@*RESULTS@#Compared with the SAH group, Sch B significantly improved the neurological function, reduced brain water content, Evan's blue content, and apoptotic cells number in the brain of rats (P<0.05 or P<0.01). Moreover, Sch B decreased SAH-induced expressions of Iba-1 and MPO (P<0.01). SAH caused the elevated expressions of Bax, Caspase-3, NLRP3, ASC, Caspase-1, IL-1β, and IL-18 in the rat brain (P<0.01), all of which were inhibited by Sch B (P<0.01). In addition, Sch B increased the Bcl-2 expression (P<0.01).@*CONCLUSION@#Sch B attenuated SAH-induced EBI, which might be associated with the inhibition of neuroinflammation, neuronal apoptosis, and the NLRP3 inflammatory signaling pathway.

El déficit de vitamina D en pacientes con espondiloartritis en un hospital de Castilla-La Mancha / Vitamin D deficiency in patients with spondylarthritis in a Spanish (Castilla-La Mancha) hospital

RESUMEN Introducción: Las espondiloartritis son un grupo de enfermedades inflamatorias crónicas con afectación principalmente del esqueleto axial y también de articulaciones periféricas. En cuanto al metabolismo óseo de estos pacientes, se ha observado en algunos estudios que existen niveles más bajos de vitamina D en pacientes con espondiloartritis. Objetivo: Estimar la prevalencia de déficit/insuficiencia de vitamina D, el metabolismo fosfocálcico y sus implicaciones en una cohorte de pacientes con espondiloartritis. Metodología: Estudio observacional, descriptivo y transversal. Se llevó a cabo una revisión retrospectiva de la base de datos de pacientes con espondiloartritis que fueron atendidos en las consultas externas del Servicio de Reumatología del Hospital General Universitario de Ciudad Real entre junio del 2018 y junio del 2019. Las variables se describieron usando medidas de frecuencia o medidas de tendencia central/dispersión según correspondiera. Resultados: Se analizaron 115 pacientes, de los cuales 64 fueron hombres y 51 mujeres, con una edad media de 45,97 años (± 13,41 DE). Del total de los pacientes, 59 presentaron espon dilitis anquilosante, 24 artropatía psoriásica, 9 artritis asociada a enfermedad inflamatoria intestinal, 12 espondiloartritis axial no radiográfica y 11 artritis reactiva. Los niveles de vitamina D fueron de 23,81 ng/ml (±10,5 DE), con un 77,4% de los pacientes con cifras de déficit/insuficiencia de vitamina D. Agrupados por el subtipo de espondiloartritis y según las cifras de déficit/insuficiencia de vitamina D, 45 pacientes tenían espondilitis anquilo sante, 19 artropatía psoriásica, 9 artritis asociada a enfermedad inflamatoria intestinal, 7 espondiloartritis axiales no radiográficas y 9 artritis reactivas. Además, el déficit de vita mina D (< 20 ng/ml) se presentaba la mayoría de las veces en las estaciones de primavera e invierno, con 31 y 26 pacientes respectivamente. Conclusiones: Una optimización de los niveles de vitamina D puede implicar una mejoría en la situación clínica del paciente, medida tanto por BASDAI y DAPSA como por PCR y VSG. En consecuencia, se recomienda la monitorización y suplementación de vitamina D en pacientes con hipovitaminosis D.

ABSTRACT Introduction: Spondyloarthritis is a group of chronic inflammatory diseases that mainly affect the axial skeleton, and also the peripheral joints. In bone metabolism studies on these patients, it has been observed that there are lower levels of vitamin D in patients with spondyloarthritis. Objective: To estimate the prevalence of vitamin D deficiency / insufficiency, as well as calcium/ phosphate metabolism and their implications in a cohort of patients with spondyloarthritis. Methodology: Observational, descriptive, and cross-sectional study. A retrospective review of the databases was carried out on patients with spondyloarthritis who were treated in the outpatient clinics of the Rheumatology Department of the General University Hospital of Ciudad Real between June 2018 and June 2019. Variables are described using frequency and central tendency / dispersion measurements as appropriate. Results: The study included 115 patients, of whom 64 were men and 51 women, with a mean age of 45.97 years (± 13.41 SD). They included 59 patients with ankylosing spondylitis, 24 with psoriatic arthropathy, 9 arthritis associated with inflammatory bowel disease, 12 non-radiographic axial spondylarthritis, and 11 reactive arthritis. Vitamin D levels were 23.81 ng/ml (± 10.5 SD), with 77.4% of patients with vitamin D deficiency / insufficiency levels. Grouped by the spondylarthritis subtype, and according to vitamin D deficiency / insufficiency, 45 patients had ankylosing spondylitis, 19 psoriatic arthropathy, 9 arthritis associated with inflammatory bowel disease, 7 non-radiographic axial spondyloarthritis, and 9 reactive arthritis. Furthermore, vitamin D deficiency (< 20 ng/ml) mainly occurred in the spring and winter seasons, with 31 and 26 patients, respectively. Conclusions: An optimization of vitamin D levels may lead to an improvement in the clinical situation of the patients, as measured by both BASDAI and DAPSA, as well as by PCR and ESR. Therefore, vitamin D monitoring and supplementation is recommended in patients with vitamin D deficiency.

Preparation and evaluation of schisandrin B-loaded F127 modified lipid-polymer nanoparticles for inhibition of breast cancer lung metastasis / 中国中药杂志

In the current study, schisandrin B(SchB)-loaded F127 modified lipid-polymer hybrid nanoparticles(SchB-F-LPNs) were developed to improve the inhibition of breast cancer lung metastasis. Modified nanoprecipitation method was used to prepare SchB-F-LPNs. The nanoparticles were spherical in shape with shell-core structure by TEM observation. SchB-F-LPNs showed a mean particle size of(234.60±6.11) nm with zeta potential of(-5.88±0.49) mV. XRD results indicated that SchB existed in the nanoparticles in an amorphous state. The apparent permeability coefficient through porcine mucus of F-LPNs was 1.43-fold of that of LPNs as shown in the in vitro mucus penetration study. The pharmacokinetics study showed that the C_(max) of SchB was(369.06±146.94) μg·L~(-1),(1 121.34±91.65) μg·L~(-1) and(2 951.91±360.53) μg·L~(-1) respectively in SchB suspensions group, SchB-LPNs group and SchB-F-LPNs group after oral administration in rats. With SchB suspensions as the reference formulation, the relative bioavailability of SchB-F-LPNs was 568.60%. SchB-F-LPNs inhibited the morphological change during transforming growth factor-β1(TGF-β1)-induced epithelial-mesenchymal transition. In addition, SchB-F-LPNs significantly decreased the number of metastatic pulmonary nodules in 4 T1 tumor-bearing mice, suggesting that SchB-F-LPNs may inhibit the metastasis of breast cancer. These results reveal the promising potential of SchB-F-LPNs in treatment of breast cancer lung metastasis.

Schizandrin A exerts anti-tumor effects on A375 cells by down-regulating H19

Malignant melanoma (MM) is one of the malignant tumors with highly metastatic and aggressive biological actions. Schizandrin A (SchA) is a bioactive lignin compound with strong anti-oxidant and anti-aging properties, which is stable at room temperature and is often stored in a cool dry place. Hence, we investigated the effects of SchA on MM cell line A375 and its underlying mechanism. A375 cells were used to construct an in vitro MM cell model. Cell viability, proliferation, apoptosis, and migration were detected by Cell Counting Kit-8, BrdU assay, flow cytometry, and transwell two-chamber assay, respectively. The cell cycle-related protein cyclin D1 and cell apoptotic proteins (Bcl-2, Bax, cleaved-caspase-3, and cleaved-caspase-9) were analyzed by western blot. Alteration of H19 expression was achieved by transfecting with pEX-H19. PI3K/AKT pathway was measured by detecting phosphorylation of PI3K and AKT. SchA significantly decreased cell viability in a dose-dependent manner. Furthermore, SchA inhibited cell proliferation and cyclin D1 expression. SchA increased cell apoptosis along with the up-regulation of pro-apoptotic proteins (cleaved-caspase-3, cleaved-caspase-9, and Bax) and the down-regulation of anti-apoptotic protein (Bcl-2). Besides, SchA decreased migration and down-regulated matrix metalloproteinases (MMP)-2 and MMP-9. SchA down-regulated lncRNA H19. Overexpression of H19 blockaded the inhibitory effects of SchA on A375 cells. SchA decreased the phosphorylation of PI3K and AKT while H19 overexpression promoted the phosphorylation of PI3K and AKT. SchA inhibited A375 cell growth, migration, and the PI3K/AKT pathway through down-regulating H19.

Evaluation of neuroactive effects of ethanol extract of Schisandra chinensis, Schisandrin, and Schisandrin B and determination of underlying mechanisms by zebrafish behavioral profiling / 中国天然药物

Schisandra chinensis, a traditional Chinese medicine (TCM), has been used to treat sleep disorders. Zebrafish sleep/wake behavioral profiling provides a high-throughput platform to screen chemicals, but has never been used to study extracts and components from TCM. In the present study, the ethanol extract of Schisandra chinensis and its two main lignin components, schisandrin and schisandrin B, were studied in zebrafish. We found that the ethanol extract had bidirectional improvement in rest and activity in zebrafish. Schisandrin and schisandrin B were both sedative and active components. We predicted that schisandrin was related to serotonin pathway and the enthanol extract of Schisandra chinensis was related to seoronin and domapine pathways using a database of zebrafish behaviors. These predictions were confirmed in experiments using Caenorhabditis elegans. In conclusion, zebrafish behavior profiling could be used as a high-throughput platform to screen neuroactive effects and predict molecular pathways of extracts and components from TCM.

Evaluation of neuroactive effects of ethanol extract of Schisandra chinensis, Schisandrin, and Schisandrin B and determination of underlying mechanisms by zebrafish behavioral profiling / 中国天然药物

Schisandra chinensis, a traditional Chinese medicine (TCM), has been used to treat sleep disorders. Zebrafish sleep/wake behavioral profiling provides a high-throughput platform to screen chemicals, but has never been used to study extracts and components from TCM. In the present study, the ethanol extract of Schisandra chinensis and its two main lignin components, schisandrin and schisandrin B, were studied in zebrafish. We found that the ethanol extract had bidirectional improvement in rest and activity in zebrafish. Schisandrin and schisandrin B were both sedative and active components. We predicted that schisandrin was related to serotonin pathway and the enthanol extract of Schisandra chinensis was related to seoronin and domapine pathways using a database of zebrafish behaviors. These predictions were confirmed in experiments using Caenorhabditis elegans. In conclusion, zebrafish behavior profiling could be used as a high-throughput platform to screen neuroactive effects and predict molecular pathways of extracts and components from TCM.

Physical inactivity and anthropometric measures in schoolchildren from Paranavaí, Paraná, Brazil / Inatividade física e medidas antropométricas em escolares de Paranavaí, Paraná, Brasil

OBJECTIVE: To investigate the association between physical inactivity and anthropometric measures in schoolchildren from Paranavaí-Parana, Brazil. METHODS: Cross-sectional survey, carried out in July and August 2013. Sample of 566 students (287 boys and 279 girls) from 6th to 9th grade, aged 10 to 14 years, from public and private schools of Paranavaí - PR, Southern Brazil. The variables analyzed were: time of weekly physical activity through a questionnaire (physical inactivity <300 minutes/week), body mass index (BMI) and waist circumference (WC). In the statistical analysis, the U Mann-Whitney and Student's t tests were used for comparison between genders. To identify factors associated with insufficient levels of physical activity, univariate and multivariate logistic regression analysis was applied and expressed in Odds ratio (OR) and 95% confidence interval (95%CI). RESULTS: There was an association between physical inactivity and anthropometric measurements for BMI (p<0.001) and WC (p<0.001), with a prevalence rate of 56.1% and 52.7% of inactive adolescents, respectively. In the multivariate analysis, there was significant association of physical inactivity and overweight (OR 1.8, 95%CI: 1.1-3.0) and with increased waist circumference (OR 2.8, 95%CI: 1.4-3.8). CONCLUSIONS: Inadequate levels of physical activity is a determining factor for overweight and abdominal adiposity. Accordingly, preventive measures should be taken, especially in schools, emphasizing the importance of exercise for body composition control and weight reduction. .

OBJETIVO: Investigar a associação entre a inatividade física e medidas antropométricas em escolares de Paranavaí, Paraná, Brasil. MÉTODOS: Pesquisa com delineamento transversal, feita em julho e agosto de 2013. Amostra composta por 566 escolares (287 meninos e 278 meninas), de 10 a 14 anos, do 6° ao 9° ano da rede pública e privada de Paranavaí (PR). As variáveis analisadas foram: tempo de atividade física semanal, por meio de questionário (inatividade física: < 300 min/semanal), índice de massa corporal (IMC) e circunferência de cintura (CC). Na análise estatística foram usados os testes U de Mann-Whitney e t de Student para comparar os sexos. Para verificar os fatores associados ao nível insuficiente de atividade física aplicou-se o modelo de regressão logística binária univariada e multivariada, expressa em odds ratio (OR), e intervalo de confiança de 95% (IC95%). RESULTADOS: Houve associação entre inatividade física e as medidas antropométricas para IMC (p<0,001) e CC (p<0,001), com prevalências de 56,1% e 52,7% de inativos, respectivamente. Na análise multivariada, foram observadas associações significativas de inatividade física nos alunos que apresentaram excesso de peso (OR 1,8; IC95%: 1,1-3,0) e circunferência de cintura aumentada (OR 2,2; IC95%: 1,4-3,8). CONCLUSÕES: Nível inadequado de atividade física é fator determinante no excesso de peso e na adiposidade abdominal. Nesse sentido, medidas preventivas devem ser tomadas, principalmente nas escolas, e enfatizar-se a importância do exercício físico no controle da composição corporal e redução do pesoe. .

Network pharmacology-based prediction and verification of the molecular targets and pathways for schisandrin against cerebrovascular disease / 中国天然药物

AIM@#To illuminate the molecular targets for schisandrin against cerebrovascular disease based on the combined methods of network pharmacology prediction and experimental verification.@*METHOD@#A protein database was established through constructing the drug-protein network from literature mining data. The protein-protein network was built through an in-depth exploration of the relationships between the proteins. The computational platform was implemented to predict and extract the sensitive sub-network with significant P-values from the protein-protein network. Then the key targets and pathways were identified from the sensitive sub-network. The most related targets and pathways were also confirmed in hydrogen peroxide (H2O2)-induced PC12 cells by Western blotting.@*RESULTS@#Twelve differentially expressed proteins (gene names: NFKB1, RELA, TNFSF10, MAPK1, CHUK, CASP8, PIGS2, MAPK14, CREB1, IFNG, APP, and BCL2) were confirmed as the central nodes of the interaction network (45 nodes, 93 edges). The NF-κB signaling pathway was suggested as the most related pathway of schisandrin for cerebrovascular disease. Furthermore, schisandrin was found to suppress the expression and phosphorylation of IKKα, as well as p50 and p65 induced by H2O2 in PC12 cells by Western blotting.@*CONCLUSION@#The computational platform that integrates literature mining data, protein-protein interactions, sensitive sub-network, and pathway results in identification of the NF-κB signaling pathway as the key targets and pathways for schisandrin.

Prevention against and treatment of doxorubicin-induced acute cardiotoxicity by dexrazoxane and schisandrin B / 药学学报

In this study, it is to compare the effectiveness of prevention against and treatment of doxorubicin (DOX) induced cardiotoxicity by dexrazoxane and schisandrin B (Sch B) in rats. Sprague-Dawley (SD) rats were randomly divided into the following 6 groups: normal saline group, DOX group, DOX+DEX group, DOX+Sch B (80 mg x kg(-1)) group, DOX+Sch B (40 mg x kg(-1)) group and DOX+Sch B (20 mg x kg(-1)) group. The results showed that Sch B could combat the increase of myocardial enzymes in peripheral blood, decrease of the enzyme activity of myocardial tissue antioxidant enzymes and disorders of systolic and diastolic function of heart in rats intravenously injected with doxorubicin (15 mg x kg(-1)). Sch B was better than DEX in protecting rat against DOX-induced the symptoms. Sch B could protect rat against DOX-induced acute cardiomyopathy and has clinical potential applications.

Determination of five components in rongxin pills by HPLC / 中国中药杂志

To establish a method for determination contents of schizandrin, tanshinone I, cryptotanshinone, tanshinone II (A) and schizandrin B in rongxin pills. The HPLC method was performed on an Agilent C18. The mobile phase was composed of methnol and water wish gradient elution. The flow rate was 1.0 mL x min(-1). The column temperature was 30 degrees C and the detection wavelength wash 240 nm. The linear of schizandrin, tanshinone I, cryptotanshinone, Tanshinone II (A) and schizandrin B were 3.000-48.00 (r = 1.000), 3.985-63.76 (r = 0.999 9), 6.370-101.9 (r = 1.000), 8.690-139.0 (r = 0.999 9), 1.700-27.20 mg x L(-1) (r = 0.999 9), respectively. The average recoveries were 98.44%, 100.3%, 99.29%, 99.07%, 98.42%, and RSDs were 0.61%, 1.1%, 0.52%, 0.72%, 0.97%. The method is convenient, accurate and has good precision. It can be used for determination of the preparation.

Effect of forchlorfenuron on fruit morphology and lignans content of Schisandra chinensis / 中国中药杂志

The effect of plant growth regulator forchlorfenuron (CPPU) 1 x 10(-6), 0.67 x 10(-6), 0.5 x 10(-6) on fruit morphology and effective components lignans was studied. Those morphologies were the combination of four basic morphological changes. The result showed, diametre were increased and longitudinal diametre of fruits were inhibited by foliage fertilizers including CPPU. At the same time, 1 000-grain weight and yield showed the varying degrees increase under CPPU. The order of the degree was 0.5 x 10(-6) > 1 x 10(-6) > 0.67 x 10(-6). Six lignans content of Schisandra chinensis of different harvest time and different CPPU processing groups were determined, the results showed that lignans accumulation occurred mainly in periods of premature the half mature fruiting stages. Under the 0.67 x 10(-6) CPPU treatment, schisandrol B, schisandrin B, schisandrin C content of S. chinensis showed different increase.

High performance preparation and structural confirmation of lignans from Schisandrae chinensis fructus by using HSCCC combined with ESI-MSn method / 药学学报

High-speed counter-current chromatography (HSCCC) was used to high performance separate and prepare lignans from Schisandrae chinensis fructus. The solvent system is composed of n-hexane-ethyl acetate-methanol-water (9 : 1 : 5 : 5) and n-hexane-ethyl acetate-methanol-water (9 : 1 : 9 : 5), speed is at 900 r.min-1, and flow rate is at 2.0 mL.min-1. Five fractions from Schisandrae chinensis fructus extract were separated and prepared with one HSCCC process. They were identified as schisandrin, gomisin J, schisandrol B, schisantherin A and deoxyschizandrin by electrospray ionization-multiple tandem mass spectrometry (ESI-MSn), respectively. Their contents were obtained in 98.74%, 94.32%, 99.53%, 94.23% and 98.68% by ultra high performance liquid chromatography (UPLC), separately. The rapid and simple method can be applied for the preparation of lignans from Schisandrae chinensis fructus.

Network analysis of ethanol precipitation process for Schisandrae chinensis fructus / 中国中药杂志

A set of central composite design experiments were designed by using four factors which were ethanol amount, ethanol concentration, refrigeration temperature and refrigeration time. The relation between these factors with the target variables of the retention rate of schizandrol A, the soluble solids content, the removal rate of fructose and the removal rate of glucose were analyzed with Bayesian networks, and ethanol amount and ethanol concentration were found as the critical process parameters. Then a network model was built with 2 inputs and 4 outputs using back propagation artificial neural networks which was optimized by genetic algorithms. The R2 and MSE from the training set were 0.983 8 and 0.001 1. The R2 and MSE from the test set were 0.975 9 and 0.001 8. The results showed that network analysis method could be used for modeling of Schisandrae Chinensis Fructus ethanol precipitation process and identify critical operating parameters.

Chemical-pharmacokinetic-pharmacodynamic fingerprints of Schisandra chinensis alcoholic extract / 药学学报

It is valuable to establish a chemical-pharmacokinetic (PK)-pharmacodynamics (PD) fingerprint of traditional Chinese medicine (TCM) for comprehensively understanding the TCM integrated conception and revealing the material foundation. The chemical, metabolic in vitro, and PK/PD in vivo fingerprints of Schisandra chinensis (SC) alcoholic extract were established and comparatively analyzed using HPLC-UV-MS method, rat liver microsomes in vitro and CCl4 intoxicated rats in vivo. Four known effective lignans, schisandrin, schisantherin A, deoxyschizandrin and gamma-schisandrin, were detected as the standard references in SC alcoholic extract with high concentration. SC alcoholic extract and four lignans when incubated with rat liver microsomes produced several metabolites in NAPDH-dependent manner. Chemical fingerprint of some components with bioactivities were also identified in PK and PD fingerprints in normal and ALI rats that explained the material foundation of SC alcoholic extract for multiple pharmacological effects. Schisandrin, schisantherin A, deoxyschizandrin and gamma-schisandrin could be considered as the "PK marker" of SC alcoholic extract or its relevant preparations, while two metabolites of the four lignans, 7, 8-dihydroxy-schizandrin and another one (M(W) 432), could be recognized as drug-metabolism (DM) Marker. This work provides experimental data for the further studies of metabolism or material foundation of SC components.

Schisandrin B protects against nephrotoxicity induced by cisplatin in HK-2 cells via Nrf2-ARE activation / 药学学报

This study is to investigate the protection effect of schisandrin B (Sch B) against oxidation stress of HK-2 cells induced by cisplatin and the mechanisms involved. HK-2 cells were cultured and divided into different groups: solvent control group, cisplatin exposure group, positive group, Sch B treatment group. Cell viability and toxicity were evaluated by MTT and LDH assay. GSH level and SOD enzymes activities were also measured. DCFH-DA as fluorescence probe was used to detect ROS level by fluorescence microplate reader. Nrf2 translocation was detected by Western blotting. Real time Q-PCR was used to detect expressions of NQO1, HO-1 and GCLC mRNA level. The results showed that Sch B could significantly inhibit the decline of cell viability induced by cisplatin treatment (P < 0.05) and the protective effect was in a dose dependent manner. Furthermore, Sch B treatment significantly inhibited the increase of ROS level induced by cisplatin and reversed the decrease of GSH level (P < 0.05). When Sch B concentration was up to 5 micromol x L(-1), SOD enzyme activities were also enhanced significantly compared with that of the cisplatin group (P < 0.05). It was shown that Sch B could cause nuclear accumulation of Nrf2 in association with downstream activation of Nrf2 mediated oxidative response genes such as GCLC, NQO1 and HO-1. These results suggested Sch B could protect against the oxidative damage of HK-2 cells induced by cisplatin via the activation of Nrf2/ARE signal pathway.

Effect of schizandrin B on H(2)O(2)-induced apoptosis of human hepatocytes in vitro: role of Fas pathway / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of Fas pathway in H(2)O(2)-induced apoptosis of L02 human hepatocytes and the effect of schisandrin B on Fas pathway.</p><p><b>METHODS</b>Real-time quantitative PCR was used to detect the expressions of FAS, fas associated death domain protein (FADD) and caspase-8 mRNA in L02 cells exposed to H(2)O(2). Flow cytometry was employed to assess the cell apoptosis. ELISA, Western blotting and spectrophotometric assay were performed to determine the expressions of FAS protein, FADD protein and caspase-8 activity.</p><p><b>RESULTS</b>Within the dose range of 5-15 mol/L, schisandrin B dose-dependently inhibited FAS and FADD expressions and caspase-8 activation.</p><p><b>CONCLUSION</b>Schisandrin B can partially inhibit H(2)O(2)-induced L02 cell apoptosis possibly by affecting the FAS-FADD-caspase-8 pathway.</p>

Simultaneous quantitative analysis of four lignanoids in Schisandra chinensis by quantitative analysis of multi-components by single marker / 药学学报

The aim of the study is to establish a new method of quality evaluation and validate its feasibilities by the simultaneous quantitative assay of four lignanoids in Schisandra chinensis. A new quality evaluation method, quantitative analysis of multi-components by single marker (QAMS), was established and validated with Schisandra chinensis. Four main lignanoids, schisandrin, schisantherin A, deoxyschizandrin and gamma-schizandrin, were selected as analytes and schisandrin as internal reference substance to evaluate the quality. Their contents in 13 different batches of samples, collected from different bathes, were determined by both external standard method and QAMS. The method was evaluated by comparison of the quantitative results between external standard method and QAMS. No significant differences were found in the quantitative results of four lignanoids in 13 batches of S. chinensis determined by external standard method and QAMS. QAMS is feasible for determination of four lignanoids simultaneously when some authentic standard substances were unavailable, and the developed method can be used for quality control of S. chinensis.

Future of Helicobacter pylori Eradication-New Trials

The efficacy of standard 7~14 day triple therapy is decreasing, mainly due to increased primary bacterial resistance to antibiotics. Recent published studies have therefore focused on developing alternative strategies for first-line eradication of Helicobacter pylori. Clear evidence now exists that levofloxacin is a viable option for first-line therapy. In addition, data have emerged that the probiotic Saccharomyces boulardii and Lactobacillus supplementation may be a useful adjunct to antibiotic therapy. Among the novel molecules, benzimidazole-derivatives, polycyclic compounds, pyloricidin, and arylthiazole analogues seem to be the most promising. The sequential and 'concomitant' regimes have also been studied in new settings and may have a role in future algorithms. Other studies promote individualized therapies based on host polymorphisms, age, and other demographic factors and resistance. In the near future, tailored therapy could optimize eradication regimens within the different countries. This article reviews the literature published pertaining to new clinical trials of H. pylori eradication.