Competitive CatSper Activators of Progesterone from Rhynchosia volubilis.

The root Rhynchosia volubilis was widely used for contraception in folk medicine, although its molecular mechanism on antifertility has not yet been revealed. In human sperm, it was reported that the cation channel of sperm, an indispensable cation channel for the fertilization process, could be regulated by various steroid-like compounds in plants. Interestingly, these nonphysiological ligands would also disturb the activation of the cation channel of sperm induced by progesterone. Therefore, this study aimed to explore whether the compounds in R. volubilis affect the physiological regulation of the cation channel of sperm. The bioguided isolation of the whole herb of R. volubilis has resulted in the novel discovery of five new prenylated isoflavonoids, rhynchones A - E (1:  - 5: ), a new natural product, 5'-O-methylphaseolinisoflavan (6: ) (1H and 13C NMR data, Supporting Information), together with twelve known compounds (7:  - 18: ). Their structures were established by extensive spectroscopic analyses and drawing a comparison with literature data, while their absolute configurations were determined by electronic circular dichroism calculations. The experiments of intracellular Ca2+ signals and patch clamping recordings showed that rhynchone A (1: ) significantly reduced cation channel of sperm activation by competing with progesterone. In conclusion, our findings indicat that rhynchone A might act as a contraceptive compound by impairing the activation of the cation channel of sperm and thus prevent fertilization.

[The Relationship Between Quality of Life and Psychological and Behavioral Factors in Patients With Heart Failure Following Cardiac Resynchronization Therapy].

BACKGROUND: While cardiac resynchronization therapy improves the quality of life of patients with heart failure, some psychological and behavioral factors still affect the quality of life of these patients. However, information on the factors that affect the quality of life of these patients is limited. PURPOSE: To describe the quality of life and investigate the relationship between quality of life and behavioral and psychological factors such as depression, smoking, drinking, water and sodium restrictions, exercise, and adherence in patients with chronic heart failure following cardiac resynchronization therapy. METHODS: This cross-sectional study was conducted using the Morisky Medication Adherence Scale, Minnesota Living With Heart Failure Questionnaire, and Cardiac Depression Scale. A convenience sample of 141 patients with heart failure following cardiac resynchronization therapy were recruited from a tertiary academic hospital in Chengdu. RESULTS: The mean overall score of the Minnesota Living With Heart Failure Questionnaire was 30.89 (out of a total possible score of 105). Water restrictions, sodium restrictions, depression, and exercise were all shown to significantly predict quality of life among the participants. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: This paper describes the quality of life and defines the behavioral factors that affect the quality of life of patients with heart failure following cardiac resynchronization therapy. The findings suggest that nurses should manage and conduct health education for patients in order to improve their quality of life.

Betulin from Hedyotis hedyotidea ameliorates concanavalin A-induced and T cell-mediated autoimmune hepatitis in mice.

Hedyotis hedyotidea has been used in traditional Chinese medicine for the treatment of autoimmune diseases. However, the mechanisms underlying for the effect remain unknown. We previously showed that, among 11 compounds extracted from H hedyotidea, betulin produced the strongest suppressive effect on T cell activation. Here, we examined the hepatoprotective effects of betulin against acute autoimmune hepatitis in mice and the mechanisms underlying the effects. Freshly isolated mouse splenocytes were stimulated with concanavalin A (Con A, 5 µg/mL) in the presence of betulin, the cell proliferation was assessed with CSFE-dilution assay. Mice were injected with betulin (10, 20 mg·kg-1·d-1, ip) for 3 d. One hour after the last injection, the mice were injected with Con A (15 mg/kg, iv) to induce acute hepatitis. Blood samples and liver tissues were harvested at 10 h after Con A injection, and serum transaminase levels and liver histopathology were detected; serum levels of proinflammatory cytokines, hepatic T lymphocyte ratios, and functional statuses of conventional T and NKT cells were also analyzed. Betulin (16 and 32 µmol/L) dose-dependently suppressed the proliferation of Con A-stimulated mouse splenocytes in vitro. In Con A-challenged mice, preinjection with betulin (20 mg·kg-1·d-1) significantly decreased the levels of proinflammatory cytokines IFN-γ, TNF-α and IL-6, and ameliorated liver injury. Furthermore, pretreatment with betulin (20 mg·kg-1·d-1) significantly inhibited the Con A-induced activation of NKT and conventional T cells, and decreased production of proinflammatory cytokines IFN-γ, TNF-α and IL-6 in these two cell populations. Betulin has immunomodulatory effect on overly activated conventional T and NKT cells and exerts hepatoprotective action in mouse autoimmune hepatitis. The findings provide evidence for the use of H hedyotidea and its constituent betulin in the treatment of autoimmune diseases.

[Correlation Between Nursing Work Environment and Nurse Burnout, Job Satisfaction, and Turnover Intention in the Western Region of Mainland China].

BACKGROUND: Nurse burnout and low job satisfaction are main reasons that cause nurses to leave their current position. Improving the nursing work environment may reduce the severity of job burnout and of job dissatisfaction and thus decrease the turnover intention of nursing staff. PURPOSE: The aim of this study was to explore the correlation between the nursing work environment and the outcome variables of burnout, job satisfaction, and turnover intention in the western region of Mainland China. METHODS: This is a cross-sectional descriptive study. Survey data were collected between February and December 2012 from 1,112 clinical nurses working at 83 medical, surgical, and intensive care units in 20 hospitals across the western region of Mainland China. Multistage sampling was conducted on some of the participants. The research instruments that were used included the Practice Environment Scale of the Nursing Work Index, Maslach Burnout Inventory, Nurse Job Satisfaction Scale, and the self-developed basic information and turnover intention questionnaire. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 19.0. The level of statistical significance was set at p<.05. RESULTS: Among the five dimensions of the nursing work environment, collegial nurse-physician relations earned the most favorable mean scores (3.57±0.68; total=4 points), whereas adequacy of staffing and resources earned the lowest (3.21±0.82). Over half of the participants (58.4%) reported experiencing a high level of emotional exhaustion (EE) burnout, 45.2% reported experiencing a high level of depersonalization (DP) burnout, and 24.6% reported experiencing a high level of personal accomplishment (PA) burnout. About 59% of the participants were satisfied with their work and 3.8% reported intention to leave. Participants in self-reported "favorable" work environments were less likely to report high burnout, less likely to report intention to leave, and more likely to report job satisfaction than their peers in self-reported "poor" work environments. The odds ratio (OR) values were 0.64 (EE), 0.66 (DP), 0.57 (PA), 0.19, and 2.26. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results of the present study support that the nursing work environment affects nurse burnout, job satisfaction, and turnover intention. Therefore, nursing managers should work to improve nursing work environments in order to reduce the turnover intent among their nursing staff.

[Risk Prediction of Feeding Intolerance in Preterm Infants].

OBJECTIVES: To identify risk factors associated with feeding intolerance (FI) in preterm infants. METHODS: Preterm infants treated in the neonatal unit of a hospital from August 2014 to January 2015 were recruited in this study. A clinical observation table was developed based on the reactive scope model. Data in relation to predictive homeostasis, reactive homeostasis, homeostatic overload, homeostatic failure and other aspects were collected and compared between those with and without FI.Alogistic regression model was established to determine predictors of FI. RESULTS: 1.A total of 207 preterm infants were included in the study: 125 male and 82 female. They had an average gestational age of (33.48±1.66) weeks (ranging from 27+2 to 37 weeks) and an average birth body mass of (2 019.55±334.38) g(ranging from 830 g to 3 120 g).2.The incidence of FI was 33.8%. FI in preterm infants often occurred during the period of being fed within 72 h.The main clinical manifestation of FI was gastric retentionin early-preterm infants and emesis in late-preterm infants.3.Gestational age, birth body mass, fetal distress, aminophylline application, intrauterine infection, breast milk feeding and interval between stools were associated with FI. Gestational age and birth body mass were found to be significant protectors of FI in the logistic regression model. FI declined with increased gestational age and birth body mass. Fetal distress, aminophylline application, and >3 d interval between stools were found to be significant risks of FI in the logistic regression model.4.The prediction model had a 92.73% forecast generation rate of return, with 97.14% sensitivity,88.32%specificity, and 91.30% accuracy. CONCLUSIONS: Low gestational age, low birth body mass, fetal distress,aminophylline application, and >3 d interval between stools are independent risk factors associate with FI. The prediction model can identify high risk cases of FI.

[Sesquiterpenes from stems of Schisandra henryi var. henryi].

The dried stems of Schisandra henryi var. henryi were extracted with 95% ethanol and the extracts were further subjected to partition, affording the ethyl acetate extracts(EtOAc Extrs.).The EtOAc Extrs.were separated and purified with silica gel and octadecyl-silylated silica gel column chromatography, preparative HPLC and preparative TLC. Thirteen known compounds were obtained and identified by spectral methods including MS and NMR, all of which were elucidated as t-cadinol(1), cadinane-4ß,5α,10ß-triol(2), cadinane-5α, 10α-diol-2-ene(3), oxyphyllenodiols A(4), 1ß, 4ß-dihydroxyeudesman-11-ene(5), cyperusol C(6), (7R)-opposit-4(15)-ene-1ß,7-diol(7), dysodensiol E(8), epi-guaidiol A(9), aromadendrane-4ß,10ß-diol(10), tricyclohumuladiol(11), caryolane-1,9ß-diol(12), and guaidiol A(13). Compounds 3, 5-10, and 13 were separated from the genus for the first time, while compounds 1-13 were separated from this species for the first time.

[Correlation Between Job Characteristics and Occupational Fatigue in Nurses].

BACKGROUND: Occupational fatigue in nurses has earned much attention in recent years. This phenomenon affects the health of nurses and threatens the safety of patients. However, few studies have reported on the correlation between job characteristics and occupational fatigue in China. PURPOSE: The present study describes the nursing job characteristics and nursing occupational fatigue situation at general hospitals in Chengdu in China and explores the correlations between job characteristics and occupational fatigue. METHODS: A cross-sectional descriptive correlation design with systematic sampling was used to recruit 923 nurses from general hospitals in Chengdu. The structural questionnaires used in this study included a personal data-sheet, Occupational Fatigue Exhaustion Recovery Scale (OFER), and Job Content Questionnaire (JCQ). Mean, percentage, independent t test, Chi-square test, Pearson correlation, and multiple linear regression analysis were employed to analyze data. RESULTS: Nurses' acute fatigue level and chronic fatigue level were high, with average scores of 60.30 ± 22.02 and 46.44 ± 23.33, respectively. All dimensions (with the exception of colleague support) correlated significantly with job characteristics and occupational fatigue. Job control, job demand, and amount of shiftwork were important predictors of both acute fatigue and chronic fatigue. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The results of the study may help the managers better understand the current situation of nurses' occupational fatigue and formulate effective measures that consider the individual characteristics of nurses and the differences in perceived job control and job demand. Furthermore, the results may help nurses better assess the causes of their work-related fatigue and facilitate coping measures in order to reduce acute and chronic fatigue.

[Chemical constituents from stems of Hedyotis hedyotidea and their immunosuppressive activity].

Hedyotis hedyotidea has been traditionally used for the treatment of arthritis, cold, cough, gastro-enteritis, headstroke, etc. But few studies have screened the active compounds from extracts of H. hedyotidea. In this study, the structure of the chemical constituents from stems of H. hedyotidea were determined and the immunosuppressive activity of the compounds was evaluated. The compounds were separated and purified with silica gel, gel column chromatographies and preparative HPLC, and their structures were identified by spectral methods such as MS and NMR. Eleven compounds were obtained and identified as(6S,9S) -vomifoliol (1), betulonic acid (2), betulinic acid (3), betulin(4), 3-epi-betulinic acid (5), ursolic acid (6), ß-sitosterol (7), stigmast-4-en-3-one (8), 7ß-hydroxysitosterol (9), (3ß,7ß) -7-methoxystigmast-5-en-3-ol (10) and morindacin (11). This is the first report of compounds 1, 2, 4, 8, 9, 10 and 11 from H. hedyotidea. Compounds 1, 2 and 8-11 were firstly isolated from the genus Hedyotis, and compounds 9 and 10 were isolated from the family Rubiaceae for the first time. The immunosuppressive activity of these compounds was tested using the lymphocyte transsormationtest. Compounds 4, 6 and 9 showed significant immunosuppressive activity.

The association of Chinese hospital work environment with nurse burnout, job satisfaction, and intention to leave.

The purpose of this study was to describe nurse burnout, job satisfaction, and intention to leave and to explore the relationship of work environment to nursing outcomes in a sample of 9,698 nurses from 181 hospitals in China. Nurses reported moderate levels of emotional exhaustion and depersonalization and high levels of reduced personal accomplishment. Nearly one-fifth of the nurses reported high levels of burnout on all three dimensions. Forty-five percent of the nurses were dissatisfied with their current job; these nurses were most dissatisfied with their salary. Five percent of nurses reported an intention to leave. Nurses reporting mixed and good work environments were less likely to report high burnout, job dissatisfaction, and intention to leave compared with those in poor work environments. The results suggest that high burnout and low job satisfaction are prominent problems for Chinese nurses, and improving work environment might be an effective strategy for better nursing outcomes in Chinese hospitals.

The volatile oil of Hyssopus cuspidatus Boriss. (HVO) ameliorates OVA-induced allergic asthma via inhibiting PI3K/Akt/JNK/P38 signaling pathway and maintaining airway barrier integrity.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyssopus cuspidatus Boriss., a classic Uyghur medicine, is used to treat inflammatory lung diseases such as asthma. But the therapeutic effect and mechanism of the volatile oil of Hyssopus cuspidatus Boriss.(HVO) in asthma therapy remain unclear. AIM OF THE STUDY: We aim to characterize the constituents of HVO, investigate the therapeutic effect in OVA-induced allergic asthmatic mice and further explore the molecular mechanism. MATERIALS AND METHODS: In this study, we applied two-dimensional gas chromatography quadrupole time-of-flight mass spectrometry (GC × GC-QTOF MS) to identify the ingredients of HVO. We established OVA-induced asthmatic model to investigate the therapeutic effect of HVO. To further explore the potential molecular pathways, we used network pharmacology approach to perform GO and KEGG pathways enrichment, and then built an ingredient-target-pathway network to identify key molecular pathways. Finally, LPS-induced RAW 264.7 macrophages and OVA-induced asthmatic model were used to validate the potential signaling pathways. RESULTS: GC × GC-QTOF MS analysis revealed the presence of 123 compounds of HVO. The sesquiterpenes and monoterpenes are the main constituents. The in vivo study indicated that HVO suppressed OVA-induced eosinophilic infiltration in lung tissues, inhibited the elevation of IgE, IL-4, IL-5, and IL-13 levels, downregulated the expressions of phosphorylated PI3K, Akt, JNK and P38, and maintained epithelial barrier integrity via reducing the degradation of occludin, Zo-1, Zo-2, and E-cadherin. The in vitro study also revealed an inhibition of NO release and downregulation of phosphorylated PI3K, Akt, JNK and P38 levels. CONCLUSION: HVO alleviates airway inflammation in OVA-induced asthmatic mice by inhibiting PI3K/Akt/JNK/P38 signaling pathway and maintaining airway barrier integrity via reducing the degradation of occludin, Zo-1, Zo-2, and E-cadherin.

Effective substances and molecular mechanisms guided by network pharmacology: An example study of Scrophulariae Radix treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries.

ETHNOPHARMACOLOGICAL RELEVANCE: Scrophulariae Radix (Xuanshen [XS]) has been used for several years to treat hyperthyroidism. However, its effective substances and pharmacological mechanisms in the treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries have not yet been elucidated. AIM OF THE STUDY: This study aimed to explore the pharmacological material basis and potential mechanism of XS therapy for hyperthyroidism and thyroid hormone-induced liver and kidney injuries based on network pharmacology prediction and experimental validation. MATERIALS AND METHODS: Based on 31 in vivo XS compounds identified using ultra-performance liquid chromatography tandem quadruple exactive orbitrap high-resolution accurate-mass spectrometry (UPLC-QE-HRMS), a network pharmacology approach was used for mechanism prediction. Systematic networks were constructed to identify the potential molecular targets, biological processes (BP), and signaling pathways. A component-target-pathway network was established. Mice were administered levothyroxine sodium through gavage for 30 d and then treated with different doses of XS extract with or without propylthiouracil (PTU) for 30 d. Blood, liver, and kidney samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) and western blotting. RESULTS: A total of 31 prototypes, 60 Phase I metabolites, and 23 Phase II metabolites were tentatively identified in the plasma of rats following the oral administration of XS extract. Ninety-six potential common targets between the 31 in vivo compounds and the diseases were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that Bcl-2, BAD, JNK, p38, and ERK1/2 were the top targets. XS extract with or without PTU had the following effects: inhibition of T3/T4/fT3/fT4 caused by levothyroxine; increase of TSH levels in serum; restoration of thyroid structure; improvement of liver and kidney structure and function by elevating the activities of anti-oxidant enzymes catalase (CAT),superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px); activation anti-apoptotic proteins Bcl-2; inhibition the apoptotic protein p-BAD; downregulation inflammation-related proteins p-ERK1/2, p-JNK, and p-p38; and inhibition of the aggregation of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6, as well as immune cells in the liver. CONCLUSION: XS can be used to treat hyperthyroidism and liver and kidney injuries caused by thyroid hormones through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. In addition, serum pharmacochemical analysis revealed that five active compounds, namely 4-methylcatechol, sugiol, eugenol, acetovanillone, and oleic acid, have diverse metabolic pathways in vivo and exhibit potential as effective therapeutic agents.

Two new compounds from Schisandra glaucescens.

One new lignan (7S,8R,7'R,8'R)-7-(3,4-methylenedioxyphenyl)-8,8'-dimethyl-8'-hydroxyl-7'-methoxyl-7'-(3',4'-methylenedioxyphenyl)-tetrahydrofuran (1), one new sesquiterpene 2-hydroxy-11,12-dehydrocalamenene (2), one new natural product erythro-1-(3,4-dimethoxyphenyl)-4-(3,4-methylenedioxyphenyl)-2,3-dimethyl-butane (3), and two known lignans (+)-anwulignan(erythro-1-(4-hydroxy-3-methoxyphenyl)-4-(3,4-methylenedioxyphenyl)-2,3-dimethyl-butane) (4) and ( - )-zuonin-A (5) were isolated from the stems of Schisandra glaucescens Diels. Their structures were elucidated by spectroscopic methods. The cytotoxicity of compounds 1 and 2 was assayed.

Licochalcone A Induces Ferroptosis in Hepatocellular Carcinoma via Reactive Oxygen Species Activated by the SLC7A11/GPX4 Pathway.

Liver cancer is a common malignant tumor, and its incidence is increasing yearly. Millions of people suffer from liver cancer annually, which has a serious impact on global public health security. Licochalcone A (Lico A), an important component of the traditional Chinese herb licorice, is a natural small molecule drug with multiple pharmacological activities. In this study, we evaluated the inhibitory effects of Lico A on hepatocellular carcinoma cell lines (HepG2 and Huh-7), and explored the inhibitory mechanism of Lico A on hepatocellular carcinoma. First, we evaluated the inhibitory effects of Lico A on hepatocellular carcinoma, and showed that Lico A significantly inhibited and killed HepG2 and Huh-7 cells in vivo and in vitro. Transcriptomic analysis showed that Lico A inhibited the expression of solute carrier family 7 member 11 (SLC7A11), which induced ferroptosis. We confirmed through in vivo and in vitro experiments that Lico A promoted ferroptosis in hepatocellular carcinoma cells by downregulating SLC7A11 expression, thereby inhibiting the glutathione (GSH)-glutathione peroxidase 4 (GPX4) pathway and inducing activation of reactive oxygen species (ROS). In this study, we suggest that Lico A is a potential SLC7A11 inhibitor that induces ferroptotic death in hepatocellular carcinoma cells, thereby providing a theoretical basis for the development of natural small molecule drugs against hepatocellular carcinoma.

Metabolic profiling integrated with pharmacokinetics to reveal the material basis of Xiaokeyinshui extract combination in the treatment of type 2 diabetes in rats.

Xiaokeyinshui extract combination (XEC), originating from a traditional Chinese formula Xiaokeyinshui (XKYS) recorded in ancient Bencao, has been reported to exert significant hypoglycemic effects. However, the chemical profiles, metabolic transformation and pharmacokinetic behavior of XEC in vivo were unclear. The research was to investigate the chemical constituents, metabolic profiles and pharmacokinetic behavior of XEC. A UPLC-QE-Orbitrap-HRMS qualification method was developed to identify the chemical constituents in XEC and xenobiotics of XEC in plasma, urine, feces and bile of rats after oral administration. A LC-MS quantification method was established and applied for the pharmacokinetic studies of major active compounds of XEC in normal and T2DM rats and Coptidis Rhizoma extracts (CRE) in T2DM rats. Fifty eight compounds in XEC and a total of 152 xenobiotics were identified in T2DM rats, including 28 prototypes and 124 metabolites. The metabolic pathways were demethylation, demethyleneization, reduction, hydroxylation, hydrolysis and subsequent binding reactions, including glucuronidation, sulfation and methylation. According to the results of chemical constituents and metabolites, 7 ingredients, including berberine, palmatine, coptisine, epiberberine, berberrubine, magnoflorine and aurantio-obtusin were suggested for markers to comparative pharmacokinetics study in normal rats and T2DM rats. Compared with normal rats, the Tmax of berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine was significantly longer. The value of Cmax for palmatine, coptisine, epiberberine and berberrubine was significantly decreased in XEC T2DM group. The value of AUC for alkaloids was higher in diabetic rats. After oral CRE, alkaloids including berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine could be detected in vivo. Compared with T2DM rats after oral administration of CRE, the value of Tmax and Cmax for berberine, palmatine, coptisine, epiberberine, berberrubine and magnoflorine exhibited significant differences in XEC T2DM group. This research provided an overview of the chemical profiles and metabolic profiling of XEC and elucidated the effect of diabetic state and compatibility on pharmacokinetic behaviors of active components in XEC. This research also can provide the material basis of XEC for subsequent quality control research.

Nurse staffing levels make a difference on patient outcomes: a multisite study in Chinese hospitals.

PURPOSE: The purpose of this study is to examine the relationship between nurse staffing and patient outcomes in hospitals in mainland China. METHODS: The study was conducted in 181 hospitals across all of the eight economic zones in mainland China using a four-stage sampling design. Two instruments, the China Nurse Survey and the patient satisfaction measurement from the Hospital Consumer Assessment of Healthcare Providers and Systems, were employed in data collection. In this article, 7,802 nurse surveys and 5,430 patient surveys from 600 medical and surgical units were analyzed. RESULTS: The adjusted joint effects of nurse staffing on patient outcomes from logistic regression analyses showed that more nursing staff per patient had statistically significant positive effects on all necessary nursing care, nurses' reports of quality of care, their confidence on patients' self-care ability on discharge from the hospital, patient adverse events, as well as patients' report of satisfaction. When the nurse-to-patient ratio (total number of nurses on all shifts on the unit divided by total number of patients who stay on the unit) increased to the 0.5-<0.6 category, most patient outcomes were significantly improved, considering hospital and patient factors and nurse skill mix in the logistic regression models. CONCLUSIONS: The findings provide evidence on how inadequate nurse staffing might result in missed but needed nursing care and negative patient outcomes, while better staffing levels could be an effective strategy for improving patient outcomes. CLINICAL RELEVANCE: We recommend that the nurse-to-patient ratio on medical and surgical units in Chinese hospitals be increased to at least 0.5-0.6 so as to secure patient safety and the quality of health services.

[Sesquiterpenes from stem of Schisandra glaucescens].

OBJECTIVE: To study the chemical constituents from Schisandra glaucescens. METHOD: The chemical constituents were separated and purifed with silica gel, gel column chromatography preparative HPLC, and their structures were identified by such spectral methods as MS and NMR. RESULT: Twelve compounds were separated from petroleum ether fractions, and identified as t-cadinol (1), alpha-cadinol (2), torreyol (3), (+)-ent-epicubenol (4), ent-T-muurolol (5), (-)-15-hydroxycalamenene (6), (-)-cubebol (7), 4-epi-cubebol (8), caryophyllenol-I (9), caryophyllenol-II (10), oxyphyllenodiols A (11), caryolane-1,9/3-diol (12). CONCLUSION: Compounds 4, 6-12 were separated from the genus for the first time, while compounds 1-12 were separated from this plant for the first time.

GII.P16-GII.2 Recombinant Norovirus VLPs Polarize Macrophages Into the M1 Phenotype for Th1 Immune Responses.

Norovirus (NoV) is a zoonotic virus that causes diarrhea in humans and animals. Outbreaks in nosocomial settings occur annually worldwide, endangering public health and causing serious social and economic burdens. The latter quarter of 2016 witnessed the emergence of the GII.P16-GII.2 recombinant norovirus throughout Asia. This genotype exhibits strong infectivity and replication characteristics, proposing its potential to initiate a pandemic. There is no vaccine against GII.P16-GII.2 recombinant norovirus, so it is necessary to design a preventive vaccine. In this study, GII.P16-GII.2 type norovirus virus-like particles (VLPs) were constructed using the baculovirus expression system and used to conduct immunizations in mice. After immunization of mice, mice were induced to produce memory T cells and specific antibodies, indicating that the VLPs induced specific cellular and humoral immune responses. Further experiments were then initiated to understand the underlying mechanisms involved in antigen presentation. Towards this, we established co-cultures between dendritic cells (DCs) or macrophages (Mø) and naïve CD4+T cells and simulated the antigen presentation process by incubation with VLPs. Thereafter, we detected changes in cell surface molecules, cytokines and related proteins. The results indicated that VLPs effectively promoted the phenotypic maturation of Mø but not DCs, as indicated by significant changes in the expression of MHC-II, costimulatory factors and related cytokines in Mø. Moreover, we found VLPs caused Mø to polarize to the M1 type and release inflammatory cytokines, thereby inducing naïve CD4+ T cells to perform Th1 immune responses. Therefore, this study reveals the mechanism of antigen presentation involving GII.P16-GII.2 recombinant norovirus VLPs, providing a theoretical basis for both understanding responses to norovirus infection as well as opportunities for vaccine development.

Network pharmacology analysis and experimental validation to explore the mechanism of Hanchuan Zupa Granule in asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Hanchuan Zupa Granule (HCZP) is a classic prescription of Uyghur medicine, that is used for cough and abnormal mucinous asthma caused by a cold and "Nai-Zi-Lai". AIM OF THE STUDY: This study aimed to explore the possible molecular mechanism of HCZP in the treatment of asthma, using a network pharmacology method and in vivo experiments. MATERIALS AND METHODS: First, we conducted qualitative analysis of the chemical composition of HCZP as a basis for network pharmacology analysis. Using network pharmacology tools, the possible signaling pathways of HCZP in the treatment of asthma were obtained. An OVA-sensitized asthma model was established, and HCZP was continuously administered for one week. BALF was collected for cell counting, and serum and lung tissues were collected to analyze the expression of IgE, IL-4, IL-5, IL-13 and IFN-γ. Hematoxylin & eosin (H&E) staining was performed to assess the pathological changes in the lung tissues. Related protein expression in the lung tissues was analyzed by Western blotting for molecular mechanism exploration. RESULTS: Fifty-six chemical compounds were identified by UPLC Q-TOF MS. According to the network pharmacology results, 18 active compounds were identified among the 56 compounds, and 68 target genes of HCZP in the treatment of asthma were obtained. A total of 19 pathways were responsible for asthma (P < 0.05) according to KEGG pathway analysis. In vivo results showed that OVA sensitivity induced increased respiratory system resistance and inflammatory responses, which included inflammatory cell infiltration and high levels of IgE, IL-4, IL-5 and IL-13 in serum and lung tissues. Furthermore, OVA upregulated p-PI3K, p-JNK and p-p38 expression in lung tissues. Moreover, HCZP treatment significantly downregulated respiratory system resistance, and the expression of IL-4, IL-5, IL-13 and IgE, as well as significantly improved inflammatory cell infiltration in lung tissues. Moreover, the protein expression of p-PI3K, p-JNK and p-p38 in lung tissues decreased after HCZP treatment. CONCLUSION: HCZP significantly inhibited the OVA-induced inflammatory response via the PI3K-Akt and Fc epsilon RI signaling pathways.

Two new flavan-4-ol glycosides from Abacopteris penangiana.

Two new flavan-4-ol glycosides, (2R,4S)-6,8-dimethyl-7-hydroxy-4'-methoxy-4,2''-oxidoflavan-5-O-beta-D-6''-O-acetyl-glucopyranoside (1) and (2R,4S)-5,7-O-beta-D-di-glucopyranosyloxy-4'-methoxy-6,8-dimethyl-4,2''-oxidoflavane (2), were isolated from the rhizomes of Abacopteris penangiana. Their structures were elucidated by spectroscopic methods. Compounds 1 and 2 showed significant anticancer activities against HeLa and L929 cell lines in vitro.

Cytotoxic triterpene saponins from Alternanthera philoxeroides.

Four new pentacyclic triterpene saponins, philoxeroidesides A-D (1-4) were isolated from the aerial parts of Alternanthera philoxeroides. Their structures were elucidated on the basis of 1D- and 2D-NMR experiments and MS analyses. Philoxeroidesides A-D (1-4) showed cytotoxic activities against SK-N-SH and HL60 cell lines.