ABSTRACT
BACKGROUND: Patients with relapsed or refractory acute myeloid leukemia (R/R AML) and FLT3-internal tandem duplication (FLT3-ITD) respond infrequently to salvage chemotherapy. OBJECTIVE: To investigate the efficacy of sorafenib plus triplet therapy with venetoclax, azacitidine, and homoharringtonine (VAH) as a salvage therapy in this population. METHODS: This multicenter, single-arm, phase 2 study was conducted at 12 hospitals across China. Eligible patients had R/R AML with FLT3-ITD (aged 18-65 years) who were treated with VAH. The primary endpoint was composite complete remission (CRc) after two cycles. Secondary outcomes included the overall response rate (ORR), safety, and survival. RESULTS: Between July 9, 2020, and March 19, 2022, 58 patients were assessed for eligibility, 51 of whom were enrolled. The median patient age was 47 years (interquartile range [IQR] 31-57). CRc was 76.5% with ORR of 82.4%. At a median follow-up of 17.7 months (IQR, 8.7-24.7), the median duration of CRc was not reached (NR), overall survival was 18.1 months (95% confidence interval [CI], 11.8-NR) and event-free survival was 11.4 months (95% CI, 5.6-NR). Grade 3 or 4 adverse events occurring in ≥10% of patients included neutropenia in 47 (92.2%), thrombocytopenia in 41 (80.4%), anemia in 35 (68.6%), febrile neutropenia in 29 (56.9%), pneumonia in 13 (25.5%), and sepsis in 6 (11.8%) patients. Treatment-related death occurred in two (3.9%) patients. CONCLUSIONS: The sorafenib plus VAH regimen was well tolerated and highly active against R/R AML with FLT3-ITD. This regimen may be a suitable therapeutic option for this population, but larger population trials are needed to be explored. TRIAL REGISTRATION: Clinical Trials Registry: NCT04424147.
Subject(s)
Azacitidine , Bridged Bicyclo Compounds, Heterocyclic , Leukemia, Myeloid, Acute , Sulfonamides , Humans , Azacitidine/therapeutic use , fms-Like Tyrosine Kinase 3/genetics , fms-Like Tyrosine Kinase 3/therapeutic use , Homoharringtonine/therapeutic use , Leukemia, Myeloid, Acute/therapy , Pathologic Complete Response , Sorafenib/adverse effects , Adolescent , Young Adult , Adult , Middle Aged , AgedABSTRACT
Dendrobium officinale (D. officinale) and Anoectochilus roxburghii (A. roxburghii) are precious raw materials for traditional Chinese medicine. The growing demand for D. officinale and A. roxburghii cannot be met by current production techniques. Hence, the widespread artificial cultivation of D. officinale and A. roxburghii using substantial amounts of plant growth regulators (PGRs) has emerged. The excessive use of PGRs not only affects the quality and efficacy of medicinal materials but also causes a series of safety issues. Therefore, expanding research on residual PGRs in valuable Chinese medicinal materials is important to avoid the health hazards caused by these substances. Unfortunately, the identification of PGRs is challenging because of their trace and complex matrices. High performance liquid chromatography (HPLC) has become one of the mainstream analytical methods for PGR determination. An important consideration in the application of this technique to the detection of trace acidic PGRs is how to improve its accuracy and sensitivity. Three-phase hollow fiber liquid phase microextraction (3P-HF-LPME) has the advantages of a high enrichment factor, complex sample purification ability, low reagent consumption, low cost, and easy integration with chromatographic systems. Thus, the 3P-HF-LPME method overcomes the many shortcomings of traditional sample pretreatment methods. In this study, a novel, simple, and effective analytical method based on 3P-HF-LPME combined with HPLC was developed to extract, purify, enrich, and detect three trace acidic PGRs (indole-3-acetic acid, naphthyl acetic acid and indolebutyric acid) in D. officinale and A. roxburghii. The chromatographic separation conditions and 3P-HF-LPME model parameters were systematically optimized for this purpose. First, the sample solution was prepared by ultrasonication and low-temperature standing, and then adjusted to pH 3.0 using dilute hydrochloric acid. The sample solution (10 mL) and NaCl (1.50 g) were stored in a 15 mL brown extraction bottle with a built-in magnetic stirrer. Next, 30 µL of NaOH solution (pH 11.0) as the inner phase solution was injected into the inner cavity of a hollow fiber tube, which was subsequently sealed at both ends. The hollow fiber tube was soaked in n-octanol for 5 min and dried naturally to remove excess extraction solvent from its surface. Finally, the fiber tube was placed in a brown extraction bottle and stirred using a thermostatic magnetic stirrer at 40 â and 1600 r/min for 2 h. After extraction, the three target analytes were separated on a Welch Ultimate XB-C18 column (250 mm×4.6 mm, 5 µm) under isocratic elution conditions using acetic acid aqueous solution and methanol (45â¶55, v/v) as the eluent. The results indicated that the three PGRs showed good linearity in the range of 0.5-100.0 µg/L (coefficients of determination (r2)=0.9999), with limits of detection (LODs) of 0.02-0.15 µg/L. The method recoveries were 88.5-102.2%, with relative standard deviations (RSDs) of less than 3.7% (n=3). The extraction efficiencies and enrichment factors of the three PGRs in 15 batches of fresh D. officinale and A. roxburghii products were found to be 42.0%-86.8% and 140-289. Full-scan mass spectrometry was used to further identify positive samples to avoid false-positive results and enhance the reliability of the experimental method. In summary, the proposed method is sensitive, accurate, reliable, environment friendly, and capable of high enrichment. It could be used to determine the residues of three acidic PGRs in D. officinale and A. roxburghii. Moreover, it can provide technical support for the residue detection of PGRs in other Chinese medicinal materials.
Subject(s)
Dendrobium , Liquid Phase Microextraction , Plant Growth Regulators/analysis , Chromatography, High Pressure Liquid , Liquid Phase Microextraction/methods , Reproducibility of ResultsABSTRACT
This study investigates the effect of progressive muscle relaxation training on negative mood and sleep quality in Coronavirus Pneumonia (COVID-19) patients.COVID-19 is an emerging infectious disease, and there is still uncertainty about when the outbreak will be contained and the effectiveness of treatments. Considering that this disease is highly contagious, patients need to be treated in isolation. This may lead to psychological symptoms such as anxiety and depression, and even sleep problems.This study is a clinical observation study.Participants included 79 COVID-19 patients admitted to a designated hospital for COVID-19 patients in Wuhan from February to March, 2020. Patients were selected and assigned to the control group and the observation group according to their wishes, with 40 and 39 cases in each group, respectively. The control group received routine treatment and nursing, and the observation group received progressive muscle relaxation training, in addition to the routine treatment and nursing. We compared scores of the Pittsburgh Sleep Quality Index Scale (PSQI), the Generalized Anxiety Disorder (GAD-7), and the Patient Health Questionnaire (PHQ-9) before and after the intervention.There was no significant difference in PSQI, GAD-7, and PHQ-9 scores between the control group and the observation group before the intervention (Pâ>â.05). After the intervention, the difference in scores of PSQI, GAD-7, and PHQ-9 in the 2 groups were statistically significant (Pâ<â.05).Progressive muscle relaxation training can significantly reduce anxiety and depression and improve sleep quality in COVID-19 patients during isolation treatment.Progressive muscle relaxation training was shown to improve the treatment effect of patients and is worthy of clinical promotion.
Subject(s)
Anxiety Disorders/therapy , Autogenic Training/methods , Betacoronavirus , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Sleep Wake Disorders/therapy , Sleep/physiology , Adult , Anxiety Disorders/virology , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/psychology , Depression/therapy , Depression/virology , Emotions/physiology , Female , Humans , Male , Middle Aged , Pandemics , Patient Health Questionnaire , Pneumonia, Viral/complications , Pneumonia, Viral/psychology , SARS-CoV-2 , Sleep Wake Disorders/virology , Surveys and Questionnaires , Treatment OutcomeABSTRACT
Based on data mining and through the method of network pharmacology, we analyzed the mechanism of high-frequency use of herb pair in the treatment of constipation with aromatic traditional Chinese medicine in this study. Through data mining, aromatic traditional Chinese medicine was obtained for the treatment of constipation and Pericarpium Citri Reticulatae and Aucklandiae Radix herb pair was used as the research object. The volatile oil from Pericarpium Citri Reticulatae and Aucklandiae Radix was extracted by steam distillation, and the chemical compositions of the volatile oil were detected by gas chromatography-mass spectrometry(GC-MS). The targets of volatile oil from Pericarpium Citri Reticulatae and Aucklandiae Radix were searched by PubChem, TCMSP, STITCH and Swiss Target Prediction databases. The targets of constipation were predicted and screened in OMIM, Genecards-Search Resuits and TTD databases. The obtained targets were introduced into Cytoscape 3.7.1 to construct protein-protein interaction(PPI) network diagram for GO and KEGG pathway enrichment analysis by using R language. The network diagram of "component-target-pathway" was constructed according to the results of KEGG enrichment. Discovery Studio 2.5 software was used to verify the molecular docking between the components and the targets. Among them, the most frequently used pair of aromatic traditional Chinese medicine in the treatment of constipation was Pericarpium Citri Reticulatae and Aucklandiae Radix. A total of 33 compounds were detected by GC-MS, and a total of 180 common action targets of Pericarpium Citri Reticulatae and Aucklandiae Radix on volatile oil in the treatment of constipation were predicted. The key targets included CYP19 A1, PPARA, PGR, ACHE, SLC6 A2 and so on. GO enrichment analysis showed that the activities of Pericarpium Citri Reticulatae and Aucklandiae Radix on volatile oil were mainly involved in the biological processes such as circulatory system, blood circulation, and steroid hormone binding. In KEGG enrichment pathway, neuroactive ligand-receptor interaction, endocrine resistance, Ca~(2+) signal pathway and IL-17 signaling pathway showed significant effect on constipation. The results of molecular docking showed that PGR, the target protein related to the treatment of constipation, had a good binding with gamma-linolenic acid, dihydro-alpha-ionone, alpha-eudesmol, caryophyllene oxide and beta-ionone. The results show that by using data mining technology and network pharmacology, it is revealed that the active components of Pericarpium Citri Reticulatae and Aucklandiae volatile oil in high frequency use of aromatic traditional Chinese medicine can be used totreat constipation mainly through CYP19 A1, PPARA, PGR, ACHE, SLC6 A2 and other targets, providing a new idea and method for the further study of aromatic traditional Chinese medicine in the treatment of constipation.
Subject(s)
Humans , Citrus , Constipation , Data Mining , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Molecular Docking SimulationABSTRACT
BACKGROUND: The objective of this study was to evaluate the effect of sorafenib on the outcomes of patients with acute myeloid leukemia (AML) with FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 144 patients with FLT3-ITD AML undergoing allo-HSCT between January 2012 and December 2015 were enrolled in this study. Depending on whether they were receiving sorafenib before transplantation or sorafenib maintenance after transplantation, patients were divided into 4 groups: patients receiving sorafenib before transplantation (group A; n = 36), patients receiving sorafenib after transplantation (group B; n = 32), patients receiving sorafenib both before and after transplantation (group C; n = 26), and patients receiving sorafenib neither before nor after transplantation (group D; n = 50). Outcomes were compared among these groups. RESULTS: The 3-year relapse rates were 22.2%, 18.8%, 15.8%, and 46.1% for groups A, B, C, and D, respectively (P = .006). The 3-year overall survival (OS) rates were 74.9%, 78.1%, 84.6%, and 50.9%, respectively (P = .023), and the 3-year leukemia-free survival (LFS) rates were 69.4%, 78.1%, 80.4%, and 34.8%, respectively (P < .001). The relapse rate was higher and the LFS was shorter in group D versus groups A, B, and C. The OS in group D was shorter than the OS in group C but was similar to the OS in groups A and B. A multivariate analysis revealed that sorafenib before transplantation, sorafenib maintenance after transplantation, and their combined application were protective factors for a lower relapse rate (hazard ratios [HRs], 0.436 [P = .048], 0.431 [P = .046], and 0.173 [P = .002], respectively) and longer LFS (HRs, 0.322 [P = .010], 0.343 [P = .014], and 0.187 [P = .001], respectively). CONCLUSIONS: Sorafenib before transplantation, sorafenib maintenance after transplantation, and their combined application all could improve the outcomes for patients with FLT3-ITD AML. Further study is needed to determine whether the use of sorafenib both before and after transplantation might be ideal. Cancer 2018;124:1954-63. © 2018 American Cancer Society.
Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/therapy , Protein Kinase Inhibitors/therapeutic use , Sorafenib/therapeutic use , fms-Like Tyrosine Kinase 3/genetics , Adult , Combined Modality Therapy/methods , Disease-Free Survival , Female , Follow-Up Studies , Gain of Function Mutation , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Mutation , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/prevention & control , Protein Domains/genetics , Protein Kinase Inhibitors/pharmacology , Remission Induction/methods , Retrospective Studies , Segmental Duplications, Genomic/genetics , Sorafenib/pharmacology , Survival Rate , Tandem Repeat Sequences/genetics , Transplantation, Homologous , Young Adult , fms-Like Tyrosine Kinase 3/antagonists & inhibitorsABSTRACT
Diabetic kidney disease (DKD) is a chronic renal microvascular complication associated with abnormal glucose metabolism, which is an important cause of end stage renal disease. Diabetes can damage the kidney through many ways, including renal vascular, glomerular, tubular, and renal interstitial damages. Therefore, a comprehensive treatment process must be taken for the treatment of DKD, and the selection of appropriate drugs has important significance in the treatment of DKD. Berberine has significant curative effect in the treatment of DKD, and the mechanism is related to the reduction of blood sugar, improvement of renal hemodynamics abnormality, regulation of blood lipid profile and the attenuation of systemic and local inflammation.
ABSTRACT
Based on the principle of particle design, the powder of Xiaojin Pills was prepared, and the quality uniformity was investigated by means of powder characterizations and content uniformity. By studying the mixed crushing rules of the classified materials and the design principle of the powder particles of Chinese medicine, the powder of the Xiaojin Pills was prepared. At the same time, the manmade mixed powder and the control powder prepared by pharmacopoeia were prepared. The mixed homogeneity of the three powders was evaluated by particle size distribution and color difference. The GC-MS and LC-MS/MS were used to study the homogeneity of their contents. The best preparation process of particle design powder is:materials easily crushed are smashed for 50 min in the vibrating ultrafine mill with -15℃, then add the materials difficultly crushed into the mill and let them crushed together for 3 min. The particle size range of manmade mixed powder was the largest with the particle size difference being more than 100 microns, the RSD value being 26.07%. The particle size range was more than 50 microns in the powder prepared by pharmacopoeia, and the RSD was nearly 15%. The difference in particle size was only around 4 μm and the RSD value was 3.18%. The color difference test showed that the composite chromatism (dE*) value of the powder prepared by pharmacopoeia was the largest for the RSD was 84.56%. The RSD of manmade mixed powder and the powder prepared by Pharmacopeia were 53.83% and 32.83%, respectively. The RSD value of the particle designed powder's muscone content is about 50% of the other two kinds of powders. The contents of 10 components in powders were determined by LC-MS/MS. The RSD values of the particle designed powder were much smaller than other two kinds of powders. Results indicate that the uniformity of the particle designed powder is better than other two kinds of powders. Chinese medicine particle design technology can effectively improve the uniformity of traditional Chinese medicine powder.
ABSTRACT
WJ1376-1 and WJ1398-1 are new synthetic compounds developed based on the structure of the Chinese herbal medicine osthole. Previously, we reported that WJ1376-1 and WJ1398-1 can induce cell-cycle arrest by activating ATR kinase (ataxia telangiectasia and rad3 related kinase) and inhibiting the phosphorylation of Aurora A kinase. In this study, we determined that WJ1376-1 and WJ1398-1 strongly inhibited the migration and invasion in human colorectal cancer cells at concentrations as low as 1µM. In the transforming growth factor (TGF)-ß-induced epithelial-mesenchymal transition model, WJ1376-1 and WJ1398-1 potently downregulated the transcription factor Snail1, the mesenchymal protein vimentin, and matrix metalloprotease-9, but upregulated the epithelial protein E-cadherin. WJ1376-1 and WJ1398-1 also inhibited the TGF-ß-induced phosphorylation of Smad2 and of Akt at Ser 473, and the nuclear translocation of Smad2 was substantially lower in WJ1376-1- and WJ1398-1-treated cells than it was in control cells. In transient transfection experiments, we observed that WJ1376-1 and WJ1398-1 strongly inhibited TGF-ß-stimulated activity of a Smad reporter. Finally, WJ1376-1 and WJ1398-1 blocked TGF-ß-induced phosphorylation of the TGF-ß Type I receptor (TGF-ßRI). These results suggest that WJ1376-1 and WJ1398-1 inhibit cell migration and invasion by suppressing TGF-ßRI phosphorylation and subsequently hindering both Smad2 and phosphatidylinositol 3-kinase/Akt signaling pathways.
Subject(s)
Adenocarcinoma/drug therapy , Cell Movement/drug effects , Colorectal Neoplasms/drug therapy , Coumarins/pharmacology , Hydroxamic Acids/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Smad2 Protein/metabolism , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Cell Survival/drug effects , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Epithelial-Mesenchymal Transition/drug effects , HCT116 Cells , Humans , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/genetics , RNA/chemistry , RNA/genetics , Receptor, Transforming Growth Factor-beta Type I , Receptors, Transforming Growth Factor beta/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Smad2 Protein/genetics , Transforming Growth Factor beta/metabolismABSTRACT
<p><b>OBJECTIVE</b>To prepare andrographolide composite particles, and evaluate their particle structure and dissolution.</p><p><b>METHOD</b>The mechanical crushing method was adopted to prepare andrographolide and polyethylene glycol (PEG) 6000 composite particles. The structures were characterized by the scanning electron microscope (SEM) and the differential scanning calorimeter (DSC). The contact angles were determined by the contact angle analyzer. The in vitro dissolution curve was detected.</p><p><b>RESULT</b>Andrographolide and PEG 6000 gave rise to coated composite particle structures, with the decrease in the crystallinity of andrographolide. The in vitro dissolution rate of composite particles was significantly obvious than that of its raw materials, ultrafine powder and their physical mixtures.</p><p><b>CONCLUSION</b>Andrographolide composite particles based on the mechanical crushing method could notably enhance the in vitro dissolution of andrographolide.</p>
Subject(s)
Calorimetry, Differential Scanning , Chemistry, Pharmaceutical , Methods , Diterpenes , Chemistry , Drugs, Chinese Herbal , Chemistry , Particle Size , Solubility , Torsion, MechanicalABSTRACT
15,16-Dihydrotanshinone I (DHTS) is a component of the traditional Chinese medicinal plant Salvia miltiorrhiza Bunge. In this study, DHTS at as low as 2.5 µg/ml concentration significantly inhibited proliferation of human benign (SW480) and malignant (SW620) colorectal cancer cells, as shown by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide (MTT) and flow cytometric analysis. Activating transcription factor (ATF)-3, a basic leucine zipper-type transcription factor, was found to be predominantly up-regulated in DHTS-treated SW480 and SW620 cells. The up-regulation of ATF3 was blocked by a c-JUN N-terminal kinase (JNK) or p38 inhibitor. Overexpression of ATF3 resulted in a significant augmentation of DHTS-induced apoptosis of SW480 cells, but resistance to DHTS-induced apoptosis of SW620 cells. These results suggest that DHTS has a strong therapeutic or preventive potential against cancer. In addition, ATF3 has a dual role in DHTS-induced apoptosis, depending on the degree of malignancy of colorectal cancer.
Subject(s)
Activating Transcription Factor 3/metabolism , Apoptosis/drug effects , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Phenanthrenes/pharmacology , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Colorectal Neoplasms/enzymology , Drug Screening Assays, Antitumor , Furans , Humans , MAP Kinase Signaling System/drug effects , Mitogen-Activated Protein Kinases/metabolism , Neoplasm Metastasis , Phosphorylation/drug effects , QuinonesABSTRACT
Acupuncture possesses the antidepressant potential. In this 6-week randomized controlled trial with 4-week follow-up, 160 patients with major depressive disorder (MDD) were randomly assigned to paroxetine (PRX) alone (n = 48) or combined with 18 sessions of manual acupuncture (MA, n = 54) or electrical acupuncture (EA, n = 58). Treatment outcomes were measured mainly using the 17-item Hamilton Depression Rating Scale (HAMD-17), Self-rating Depression Scale (SDS), clinical response and remission rates. Average PRX dose taken and proportion of patients who required an increased PRX dose due to symptom aggravation were also obtained. Both additional MA and EA produced a significantly greater reduction from baseline in score on HAMD-17 and SDS at most measure points from week 1 through week 6 compared to PRX alone. The clinical response was markedly greater in MA (69.8%) and EA (69.6%) groups than the group treated with PRX alone (41.7%, P = 0.004). The proportion of patients who required an increase dose of PRX due to symptom aggravation was significantly lower with MA (5.7%) and EA (8.9%) than PRX alone (22.9%, P = 0.019). At 4 weeks follow-up after completion of acupuncture treatment, patients with EA, but not MA, continued to show significantly greater clinical improvement. Incidence of adverse events was not different in the three groups. Our study indicates that acupuncture can accelerate the clinical response to selective serotonin reuptake inhibitors (SSRIs) and prevent the aggravation of depression. Electrical acupuncture may have a long-lasting enhancement of the antidepressant effects (Trial Registration: ChiCTR-TRC-08000278).
Subject(s)
Acupuncture Therapy/methods , Combined Modality Therapy/methods , Depressive Disorder, Major/therapy , Paroxetine/pharmacology , Selective Serotonin Reuptake Inhibitors/pharmacology , Acupuncture Therapy/adverse effects , Acupuncture Therapy/instrumentation , Adult , Depressive Disorder, Major/drug therapy , Female , Follow-Up Studies , Humans , Male , Paroxetine/administration & dosage , Paroxetine/adverse effects , Psychiatric Status Rating Scales , Selective Serotonin Reuptake Inhibitors/administration & dosage , Selective Serotonin Reuptake Inhibitors/adverse effects , Time Factors , Treatment Outcome , Young AdultABSTRACT
Vitis thunbergii var. taiwaniana (VTT) is an indigenous Taiwanese wild grape and is used as a folk medicine in Taiwan. VTT is rich in polyphenols, especially quercetin and resveratrol derivatives, which were demonstrated to exhibit inhibitory activities against carcinogenesis and prevent some neurodegenerative diseases. (-)-Vitisin B is one of the resveratrol tetramers extracted from VTT. In this study, we investigated the mechanisms of (-)-vitisin B on the induction of apoptosis in human HL-60 promyelocytic leukemia cells. First, (-)-vitisin B significantly inhibited cell proliferation through inducing cell apoptosis. This effect appeared to occur in a time- and dose-dependent manner. Cell-cycle distribution was also examined, and we found that (-)-vitisin B significantly induced a sub-G1 population in a dose-dependent manner. In addition, (-)-vitisin B exhibited stronger inhibitory effects on cell proliferation than resveratrol. Second, (-)-vitisin B dose dependently induced apoptosis-related protein expressions, such as the cleavage form of caspase-3, caspase-8, caspase-9, poly(ADP ribose) polymerase, and the proapoptotic Bax protein. Third, (-)-vitisin B treatment also resulted in increases in c-Jun N-terminal kinase (JNK) phosphorylation and Fas ligand (FasL) expression. Moreover, the (-)-vitisin B-induced FasL expression and caspase-3 activation could be reversed by a JNK inhibitor. These results suggest that (-)-vitisin B-induced apoptosis of leukemia cells might be mediated through activation of JNK and Fas death-signal transduction.
Subject(s)
Antineoplastic Agents/pharmacology , Benzofurans/pharmacology , Leukemia, Promyelocytic, Acute/drug therapy , Phenols/pharmacology , Vitis/chemistry , Antineoplastic Agents/analysis , Apoptosis/drug effects , Apoptosis Regulatory Proteins , Benzofurans/analysis , Cell Cycle/drug effects , Cell Survival/drug effects , Chromatography, High Pressure Liquid , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HL-60 Cells , Humans , Leukemia, Promyelocytic, Acute/pathology , Medicine, East Asian Traditional , Phenols/analysis , Plant Extracts/analysis , Plant Extracts/pharmacology , TaiwanABSTRACT
AMP-activated protein kinase (AMPK) is an energy sensor that regulates cellular metabolism. Activation of AMPK in skeletal muscles, the liver, and adipose tissues results in a favorable metabolic milieu for preventing and treating type 2 diabetes, i.e., decreased levels of circulating glucose, plasma lipids, and ectopic fat accumulation and enhanced insulin sensitivity. Osthole was extracted from a Chinese herbal medicine, and we found that it had glucose lowering activity in our previous study. However, the detailed glucose lowering mechanisms of osthole are still unclear. In this study, we used skeletal muscle cells to examine the underlying molecular mechanisms of osthole's glucose lowering activity. A Western blot analysis revealed that osthole significantly induced phosphorylation of AMPK and acetyl-CoA carboxylase (ACC). Next, we found that osthole significantly increased the level of translocation of glucose transporter 4 (GLUT4) to plasma membranes and glucose uptake in a dose-dependent manner. Osthole-induced glucose uptake was reversed by treatment with Compound C, an AMPK inhibitor, suggesting that osthole-induced glucose uptake was mediated in an AMPK-dependent manner. The increase in the AMP:ATP ratio was involved in osthole's activation of AMPK. Finally, we found that osthole counteracted hyperglycemia in mice with streptozotocin-induced diabetes. These results suggest that the increase in the AMP:ATP ratio by osthole triggered activation of the AMPK signaling pathway and led to increases in plasma membrane GLUT4 content and glucose uptake level. Therefore, osthole might have potential as an antidiabetic agent for treating diabetes.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Coumarins/pharmacology , Glucose/metabolism , Muscle, Skeletal/enzymology , Acetyl-CoA Carboxylase/metabolism , Animals , Blood Glucose/analysis , Cell Line , Cnidium/chemistry , Coumarins/therapeutic use , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/drug therapy , Enzyme Activation/drug effects , Glucose Transporter Type 4/metabolism , Hep G2 Cells , Humans , Hyperglycemia/drug therapy , Hypoglycemic Agents , Male , Mice , Mice, Inbred ICR , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Phosphorylation/drug effects , TaiwanABSTRACT
After reviewing the literatures in recent years, it is of importance to investigate on the key brain region activated by needling with the baseline state fMRI in research of acupoint specificity and brain fMRI. It is valuable to define two ways to determine the key brain region: one is the so called Seek True, while the other one is the so called Prove Wrong, and some examples of applications of the two methods are given in order to prove that the methods are feasible on determining the key brain region.
Subject(s)
Acupuncture Therapy , Brain Mapping , Acupuncture Points , Brain/physiopathology , Humans , Magnetic Resonance ImagingABSTRACT
OBJECTIVE: To investigate the cough-relieving, analgesic and antibiotic effects of durian shell extract (DSE) in relieving cough and its analgesic and antibiotic effects. METHODS: The effect of DSE in relieving cough was assessed in mice challenged with ammonia and SO(2) to induce coughing. The analgesic and antibiotic effects of DSE in mice were evaluated by hot plate test and twisting reaction induced by acetic acid, and by minimal inhibitory concentration (MIC) and disc-agar diffusion tests, respectively. RESULTS: Compared with the control group, the mice treated with 300 and 900 mg/kg DSE showed significantly prolonged latency with decreased number of coughing induced by ammonia and SO(2), and the effect was dose-dependent. DSE markedly prolonged the latency and decreased the twisting number of the mice induced by acetic acid without affecting the pain threshold in hot plate test. DSE produced no significant inhibitory effects against Staphylococcus aureus, Staphylococcus epidermidis, or E. coli, and showed a week inhibition against Bacillus aeruginosus. CONCLUSION: DSE shows obvious effect in relieving cough and produces better analgesic effect against chemical factor-induced pain than against physical agent-induced pain sensation. DSE has a moderate inhibitory effect against Bacillus aeruginosus.
Subject(s)
Analgesics/pharmacology , Anti-Bacterial Agents/pharmacology , Antitussive Agents/pharmacology , Bombacaceae/chemistry , Plant Extracts/pharmacology , Animals , Male , Mice , Random AllocationABSTRACT
To assess the quality of randomized controlled trials (RCTs) published in Chinese Acupuncture and Moxibustion. Manually retrieve RCT papers published in Chinese Acupuncture and Moxibustion from 2000 to 2006 and use "the extraction form of acupuncture and moxibustion randomized clinical trial report data" to evaluate the quality of RCTs. Six hundred and eighty-six RCTs were enrolled. The methodological quality was lower than the international standard and only one RCT paper described the trial technological process. And there were a less reports about influencing RCT quality, such as acupuncturist's qualification and education background (3.06%), adverse reaction (4.23%), blind method (5.98%) and follow-up (14.43%). RCTs on acupuncture and moxibustion published in Chinese Acupuncture and Moxibustion need to be improved in trial design, conduction and report.
Subject(s)
Acupuncture Therapy , Moxibustion , Periodicals as Topic , Randomized Controlled Trials as Topic , Humans , Periodicals as Topic/standards , Periodicals as Topic/statistics & numerical data , Randomized Controlled Trials as Topic/standards , Randomized Controlled Trials as Topic/statistics & numerical data , Time FactorsABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of folic acid, vitamin B(6) and B(12) on plasma homocysteine and on learning and memory functions in focal cerebral ischemia rats.</p><p><b>METHODS</b>Sprague-Dawley rats were randomly divided into four groups. They were sham operation group (Sham OP), middle cerebral artery occlusion model group (MCAO), MCAO + folic acid group (MCAO + FA) and MCAO + compound vitamin (folate, vitamin B(6) and B(12)) group (MCAO + CV). Plasma homocysteine was measured before and after supplementation and after ischemia.</p><p><b>RESULTS</b>The level of plasma homocysteine in MCAO + FA and MCAO + CV groups were significantly lower than those in Sham OP and MCAO groups after supplementation and ischemia (6.92 +/- 1.04) micromol/L and (5.49 +/- 1.00) micromol/L vs (9.33 +/- 1.11) micromol/L, (10.90 +/- 2.03 micromol/L), P < 0.05. While in MCAO + CV group was lower than that in MCAO + FA group (5.49 +/- 1.00) micromol/L vs (6.92 +/- 1.04) micromol/L, P < 0.05. The neurological deficit scores and shock times in Y-type maze of MCAO + FA and MCAO + CV groups were lower than those in MCAO group (1.75 +/- 0.46 and 1.38 +/- 0.52 vs 2.62 +/- 0.52; 123.50 +/- 39.77 and 86.25 +/- 21.39 vs 173.25 +/- 46.32, P < 0.05). The correct times of MCAO + CV group in Y-type maze was higher than that in MCAO group (3.75 +/- 0.42 vs 2.12 +/- 0.45, P < 0.05).</p><p><b>CONCLUSION</b>Folic acid intake could not only reduce plasma homocysteine concentration but also promote the recovery of the learning and memory functions of rats with cerebral ischemia. The effects of folic acid combined with vitamin B(6) and vitamin B(12) on cerebral ischemia rats was better than that of single folate.</p>
Subject(s)
Animals , Female , Male , Rats , Brain Ischemia , Blood , Disease Models, Animal , Folic Acid , Pharmacology , Homocysteine , Blood , Infarction, Middle Cerebral Artery , Blood , Learning , Memory , Rats, Sprague-Dawley , Vitamin B 12 , Pharmacology , Vitamin B 6 , Pharmacology , Vitamin B Complex , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To analyze the chemical constituents of supercritical carbon dioxide extraction products from Cnidium monieri.</p><p><b>METHOD</b>Four-factor and three-level orthogonal experimental design was used to optimize the SFE conditions as guided by the content of total coumarins in the extract. The chemical constituents were separated and identified by recrystalization.</p><p><b>RESULT</b>Optimum extraction process was established: 25 MPa as extraction pressure, 50 degrees C as extraction temperature, 6.5 MPa as separation pressure and 60 degrees C as separation temperature.</p><p><b>CONCLUSION</b>Changes in extraction pressure, temperature, time, pulverized degree and separation pressure affect the extracting results remarkably. The two kinds of chemical constituents were separated by recrystallization from C. monieri and identified by the methods of UV, IR, MS, NMR.</p>
Subject(s)
Chromatography, Supercritical Fluid , Cnidium , Chemistry , Coumarins , Chemistry , Fruit , Chemistry , Furocoumarins , Chemistry , Plants, Medicinal , ChemistryABSTRACT
Objective:To investigate the association between polymorphisms of estrogen receptor ? (ER?) gene (rs3020444) and perimenopausal syndrome (PS) in patients with liver qi stagnation syndrome (LQSS). Metheds:The ER?T/C genotype in 100 patients of PS of LQSS type (PS-LQSS group),86 patients of PS of non-LSDS type (PS-non-LQSS group) and 100 healthy subjects (control) was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) assay. Results:Partitions of ?2 method showed that the higher prevalence of ER?-TT genotypes was noted in PS-LQSS group (?2=8.307,P=0.004),and the higher prevalence of T alleles was noted in PS-LQSS group (?2=7.129,P=0.008). and Multinomial logistic-regression indicated that the odds ratios (OR) of the ER?-TT genotypes vs TC/CC for PS-LQSS was 2.222 (95%CI:1.172-4.744,P=0.015) after adjusting for common miscellaneous factors. Conclusions:It was suggested that ER?-TT genotypes was significantly associated with PS-LQSS,and ESR?-TT may be one of the genes that contribute to PS-LQSS.
ABSTRACT
Hepatitis C virus (HCV) is a serious global problem, and present therapeutics are inadequate to cure HCV infection. In the present study, various antiviral assays show that As2O3 at submicromolar concentrations is capable of inhibiting HCV replication. The 50% effective concentration (EC50) of As2O3 required to inhibit HCV replication was 0.35 microM when it was determined by a reporter-based HCV replication assay, and the EC50 was below 0.2 microM when it was determined by quantitative reverse transcription-PCR analysis. As2O3 did not cause cellular toxicity at this concentration, as revealed by an MTS [3-(4,5-dimethylthiozol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay. A combination of As2O3 and alpha interferon exerted synergistic effects against HCV, as revealed by a multiple linear logistic model and isobologram analysis. Furthermore, in an alternative HCV antiviral system that may recapitulate additional steps involved in HCV infection and replication, As2O3 at 0.3 microM totally abolished the HCV signal, whereas alpha interferon at a high dose (5,000 IU/ml) only partially suppressed the HCV signal. The study highlights the indications for use of a novel class of anti-HCV agent. Further elucidation of the exact antiviral mechanism of As2O3 may lead to the development of agents with potent activities against HCV or related viruses.