Model Seleksi Premi Asuransi Jiwa Dwiguna untuk Kasus Multiple Decrement

This article discusses a select survival model for the case of multiple decrements in evaluating endowment life insurance premium for person currently aged ( + ) years, who is selected at age with ℎ years selection period. The case of multiple decrements in this case is limited to two cases. The calculation of the annual premium is done by prior evaluating of the single premium, and the present value of annuity depends on theconstant force assumption

Image5_Formononetin isolated from Sophorae flavescentis inhibits B cell-IgE production by regulating ER-stress transcription factor XBP-1.tif

RationaleIgE plays an important pathologic role in most, if not all, allergic conditions. We previously showed that ASHMI (anti-asthma herbal medicine intervention) suppressed IgE production in murine models of asthma and in asthma subjects. However, the active compounds in ASHMI responsible for the IgE suppression are still unknown.ObjectiveWe sought to identify the compound(s) in ASHMI that are responsible for IgE inhibition as well as investigate the mechanisms by which the identified compound(s) decreases IgE production.MethodsThe compounds in Sophorae Flavescentis were separated using Column chromatography and preparative-HPLC. The separated compounds were identified using LC-MS and 1H-NMR. U266 cells, an IgE-producing plasma cell line, were cultured with various concentrations of identified compounds. The levels of IgE production by the U266 cell were measured by ELISA. Trypan blue exclusion was used to determine the cell viability. The gene expression of XBP-1 and IgE-heavy chain was determined by RT-PCR.ResultsA single compound identified as formononetin was isolated from Sophorae Flavescentis. Formononetin significantly and dose dependently decreased the IgE production in U266 cells across a concentration range of 2–20 µg/ml (p ConclusionFormononetin decreased IgE production in human B cell line U266 cells in a dose-dependent fashion through the regulation of XBP-1 ER transcription. Formononetin may be a potential therapy for allergic asthma and other IgE-mediated diseases.</p

Image1_Formononetin isolated from Sophorae flavescentis inhibits B cell-IgE production by regulating ER-stress transcription factor XBP-1.tif

RationaleIgE plays an important pathologic role in most, if not all, allergic conditions. We previously showed that ASHMI (anti-asthma herbal medicine intervention) suppressed IgE production in murine models of asthma and in asthma subjects. However, the active compounds in ASHMI responsible for the IgE suppression are still unknown.ObjectiveWe sought to identify the compound(s) in ASHMI that are responsible for IgE inhibition as well as investigate the mechanisms by which the identified compound(s) decreases IgE production.MethodsThe compounds in Sophorae Flavescentis were separated using Column chromatography and preparative-HPLC. The separated compounds were identified using LC-MS and 1H-NMR. U266 cells, an IgE-producing plasma cell line, were cultured with various concentrations of identified compounds. The levels of IgE production by the U266 cell were measured by ELISA. Trypan blue exclusion was used to determine the cell viability. The gene expression of XBP-1 and IgE-heavy chain was determined by RT-PCR.ResultsA single compound identified as formononetin was isolated from Sophorae Flavescentis. Formononetin significantly and dose dependently decreased the IgE production in U266 cells across a concentration range of 2–20 µg/ml (p ConclusionFormononetin decreased IgE production in human B cell line U266 cells in a dose-dependent fashion through the regulation of XBP-1 ER transcription. Formononetin may be a potential therapy for allergic asthma and other IgE-mediated diseases.</p

Image3_Formononetin isolated from Sophorae flavescentis inhibits B cell-IgE production by regulating ER-stress transcription factor XBP-1.tif

RationaleIgE plays an important pathologic role in most, if not all, allergic conditions. We previously showed that ASHMI (anti-asthma herbal medicine intervention) suppressed IgE production in murine models of asthma and in asthma subjects. However, the active compounds in ASHMI responsible for the IgE suppression are still unknown.ObjectiveWe sought to identify the compound(s) in ASHMI that are responsible for IgE inhibition as well as investigate the mechanisms by which the identified compound(s) decreases IgE production.MethodsThe compounds in Sophorae Flavescentis were separated using Column chromatography and preparative-HPLC. The separated compounds were identified using LC-MS and 1H-NMR. U266 cells, an IgE-producing plasma cell line, were cultured with various concentrations of identified compounds. The levels of IgE production by the U266 cell were measured by ELISA. Trypan blue exclusion was used to determine the cell viability. The gene expression of XBP-1 and IgE-heavy chain was determined by RT-PCR.ResultsA single compound identified as formononetin was isolated from Sophorae Flavescentis. Formononetin significantly and dose dependently decreased the IgE production in U266 cells across a concentration range of 2–20 µg/ml (p ConclusionFormononetin decreased IgE production in human B cell line U266 cells in a dose-dependent fashion through the regulation of XBP-1 ER transcription. Formononetin may be a potential therapy for allergic asthma and other IgE-mediated diseases.</p

Image4_Formononetin isolated from Sophorae flavescentis inhibits B cell-IgE production by regulating ER-stress transcription factor XBP-1.tif

RationaleIgE plays an important pathologic role in most, if not all, allergic conditions. We previously showed that ASHMI (anti-asthma herbal medicine intervention) suppressed IgE production in murine models of asthma and in asthma subjects. However, the active compounds in ASHMI responsible for the IgE suppression are still unknown.ObjectiveWe sought to identify the compound(s) in ASHMI that are responsible for IgE inhibition as well as investigate the mechanisms by which the identified compound(s) decreases IgE production.MethodsThe compounds in Sophorae Flavescentis were separated using Column chromatography and preparative-HPLC. The separated compounds were identified using LC-MS and 1H-NMR. U266 cells, an IgE-producing plasma cell line, were cultured with various concentrations of identified compounds. The levels of IgE production by the U266 cell were measured by ELISA. Trypan blue exclusion was used to determine the cell viability. The gene expression of XBP-1 and IgE-heavy chain was determined by RT-PCR.ResultsA single compound identified as formononetin was isolated from Sophorae Flavescentis. Formononetin significantly and dose dependently decreased the IgE production in U266 cells across a concentration range of 2–20 µg/ml (p ConclusionFormononetin decreased IgE production in human B cell line U266 cells in a dose-dependent fashion through the regulation of XBP-1 ER transcription. Formononetin may be a potential therapy for allergic asthma and other IgE-mediated diseases.</p

Image2_Formononetin isolated from Sophorae flavescentis inhibits B cell-IgE production by regulating ER-stress transcription factor XBP-1.tif

RationaleIgE plays an important pathologic role in most, if not all, allergic conditions. We previously showed that ASHMI (anti-asthma herbal medicine intervention) suppressed IgE production in murine models of asthma and in asthma subjects. However, the active compounds in ASHMI responsible for the IgE suppression are still unknown.ObjectiveWe sought to identify the compound(s) in ASHMI that are responsible for IgE inhibition as well as investigate the mechanisms by which the identified compound(s) decreases IgE production.MethodsThe compounds in Sophorae Flavescentis were separated using Column chromatography and preparative-HPLC. The separated compounds were identified using LC-MS and 1H-NMR. U266 cells, an IgE-producing plasma cell line, were cultured with various concentrations of identified compounds. The levels of IgE production by the U266 cell were measured by ELISA. Trypan blue exclusion was used to determine the cell viability. The gene expression of XBP-1 and IgE-heavy chain was determined by RT-PCR.ResultsA single compound identified as formononetin was isolated from Sophorae Flavescentis. Formononetin significantly and dose dependently decreased the IgE production in U266 cells across a concentration range of 2–20 µg/ml (p ConclusionFormononetin decreased IgE production in human B cell line U266 cells in a dose-dependent fashion through the regulation of XBP-1 ER transcription. Formononetin may be a potential therapy for allergic asthma and other IgE-mediated diseases.</p

Table_1_Computational analysis to define efficacy & molecular mechanisms of 7, 4’- Dihydroxyflavone on eosinophilic esophagitis: Ex-vivo validation in human esophagus biopsies.docx

IntroductionEosinophilic Esophagitis (EoE) is a chronic condition characterized by eosinophilic inflammation of the esophagus which leads to esophageal dysfunction with common symptoms including vomiting, feeding difficulty, dysphagia, abdominal pain. Current main treatment options of EoE include dietary elimination and swallowed steroids. Diet elimination approach could lead to identifying the trigger food(s), but it often requires repeated upper endoscopy with general anesthesia and potentially could negatively affect nutrition intake and growth of the child and individuals’ quality of life. Although the swallowed steroid treatment of effective, the EoE will universally recur after discontinuation of the treatment. Digestive Tea formula (DTF) has been used by the Traditional Chinese Medicine (TCM) practice to improve GI symptoms in EoE patients, including abdominal pain, GE reflux, and abnormal bowel movement. Previously, a flavonoid small molecule compound 7, 4 dihydroxy flavone (DHF) from Glycyrrhiza uralensis in DTF inhibited eotaxin, Th2 cytokine and IgE production in vitro and in vivo.MethodThis study comprehensively evaluates the potential therapeutic and immunological mechanisms underlying DHF improvement of symptoms related to EoE using computational modeling, including target mining, gene ontology enrichment, pathway analyses, protein-protein interaction analyses, in silico molecular docking and dynamic simulation followed by ex-vivo target validation by qRT-PCR using cultured human esophagus biopsy specimen with or without DHF from patients with EoE.ResultsComputational analyses defined 29 common targets of DHF on EoE, among which TNF-α, IL-6, IL1β, MAPK1, MAPK3 and AKT1 were most important. Docking analysis and dynamic simulation revealed that DHF directly binds TNF-α with a free binding energy of -7.7 kcal/mol with greater stability and flexibility. Subsequently, in the human esophagus biopsy culture system, significant reduction in levels of TNF-α, IL-6, IL-8 and IL1-β was found in the supernatant of biopsy sample cultured with DHF. Furthermore, the gene expression profile showed significant reduction in levels of TNF-α, IL1-β, IL-6, CCND and MAPK1 in the esophagus biopsy sample cultured with DHF.DiscussionTaken together, the current study provides us an insight into the molecular mechanisms underlying multi-targeted benefits of DHF in the treatment of EoE and paves the way for facilitating more effective EoE therapies.</p

Presentation_1_Computational analysis to define efficacy & molecular mechanisms of 7, 4’- Dihydroxyflavone on eosinophilic esophagitis: Ex-vivo validation in human esophagus biopsies.pptx

IntroductionEosinophilic Esophagitis (EoE) is a chronic condition characterized by eosinophilic inflammation of the esophagus which leads to esophageal dysfunction with common symptoms including vomiting, feeding difficulty, dysphagia, abdominal pain. Current main treatment options of EoE include dietary elimination and swallowed steroids. Diet elimination approach could lead to identifying the trigger food(s), but it often requires repeated upper endoscopy with general anesthesia and potentially could negatively affect nutrition intake and growth of the child and individuals’ quality of life. Although the swallowed steroid treatment of effective, the EoE will universally recur after discontinuation of the treatment. Digestive Tea formula (DTF) has been used by the Traditional Chinese Medicine (TCM) practice to improve GI symptoms in EoE patients, including abdominal pain, GE reflux, and abnormal bowel movement. Previously, a flavonoid small molecule compound 7, 4 dihydroxy flavone (DHF) from Glycyrrhiza uralensis in DTF inhibited eotaxin, Th2 cytokine and IgE production in vitro and in vivo.MethodThis study comprehensively evaluates the potential therapeutic and immunological mechanisms underlying DHF improvement of symptoms related to EoE using computational modeling, including target mining, gene ontology enrichment, pathway analyses, protein-protein interaction analyses, in silico molecular docking and dynamic simulation followed by ex-vivo target validation by qRT-PCR using cultured human esophagus biopsy specimen with or without DHF from patients with EoE.ResultsComputational analyses defined 29 common targets of DHF on EoE, among which TNF-α, IL-6, IL1β, MAPK1, MAPK3 and AKT1 were most important. Docking analysis and dynamic simulation revealed that DHF directly binds TNF-α with a free binding energy of -7.7 kcal/mol with greater stability and flexibility. Subsequently, in the human esophagus biopsy culture system, significant reduction in levels of TNF-α, IL-6, IL-8 and IL1-β was found in the supernatant of biopsy sample cultured with DHF. Furthermore, the gene expression profile showed significant reduction in levels of TNF-α, IL1-β, IL-6, CCND and MAPK1 in the esophagus biopsy sample cultured with DHF.DiscussionTaken together, the current study provides us an insight into the molecular mechanisms underlying multi-targeted benefits of DHF in the treatment of EoE and paves the way for facilitating more effective EoE therapies.</p

DataSheet_1_Clinical efficacy of weight loss herbal intervention therapy and lifestyle modifications on obesity and its association with distinct gut microbiome: A randomized double-blind phase 2 study.docx

GoalsTo assess the efficacy and safety of Chinese Medicine Prescription “W-LHIT” in subjects with simple obesity, and to explore its potential mechanism of action.MethodsThirty-seven patients aged 18 to 60 from Wei-En hospital (Weifang City, Shandong, China), participated in a double blinded, placebo-controlled study. Subjects were randomly divided into 2 groups, 18 in treatment and 19 in placebo group. The treatment group took the “W-LHIT” capsules for two months, while the control group received placebo capsules. Both groups accepted healthy lifestyle education materials. After a 2-month treatment, the placebo group transferred to open-label treatment after unblinding.Results72.22% participants in the treatment group lost more than 5% of their body weight, compared with 36.84% in the placebo group (p ConclusionW-LHIT significantly improved body weight and comorbid conditions without obvious adverse reaction or rebound weight gain. These effects were associated with increased abundance of probiotics in gut microbiota. W-LHIT may have a potential for treating obesity in conjunction with healthy lifestyle modifications.</p

Image3_Cytochrome P450 3A4 suppression by epimedium and active compound kaempferol leads to synergistic anti-inflammatory effect with corticosteroid.tif

Introduction: Cytochrome P450 (CYP) 3A4 is a major drug metabolizing enzyme for corticosteroids (CS). Epimedium has been used for asthma and variety of inflammatory conditions with or without CS. It is unknown whether epimedium has an effect on CYP 3A4 and how it interacts with CS. We sought to determine the effects of epimedium on CYP3A4 and whether it affects the anti-inflammatory function of CS and identify the active compound responsible for this effect.Methods: The effect of epimedium on CYP3A4 activity was evaluated using the Vivid CYP high-throughput screening kit. CYP3A4 mRNA expression was determined in human hepatocyte carcinoma (HepG2) cells with or without epimedium, dexamethasone, rifampin, and ketoconazole. TNF-α levels were determined following co-culture of epimedium with dexamethasone in a murine macrophage cell line (Raw 264.7). Active compound (s) derived from epimedium were tested on IL-8 and TNF-α production with or without corticosteroid, on CYP3A4 function and binding affinity.Results: Epimedium inhibited CYP3A4 activity in a dose-dependent manner. Dexamethasone enhanced the expression of CYP3A4 mRNA, while epimedium inhibited the expression of CYP3A4 mRNA and further suppressed dexamethasone enhancement of CYP3A4 mRNA expression in HepG2 cells (p Discussion: Inhibition of CYP3A4 function by epimedium and its active compound kaempferol leads to enhancement of CS anti-inflammatory effect.</p