The phytochemical investigation of the stems of Homalium stenophyllum afforded seven new phenolic glycosides (1-5 and 8-9) and two known compounds (6 and 7). Their structures were elucidated by comprehensive analyses of NMR spectroscopic, mass spectrometric data and chemical hydrolysis. Additionally, their anti-inflammatory activities against the NO production in LPS-induced macrophages were evaluated.

In the research and development of new drugs, it is very important to investigate the in vitro metabolism of candidate drugs. Traditional models such as liver microsomes have many limitations, while the in vitro model of recombinant human drug metabolizing enzymes is considered as an important and useful approach because of its convenient access, stable activity and low cost. In this study, six major human UDP-glucuronosyltransferases (UGTs) genes (UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) were cloned from human liver cDNA and heterologously expressed in Saccharomyces cerevisiae and baculovirus-infected insect cell. UGT1A1, 1A3, 1A6 and 1A9 were successfully expressed in yeast and showed glucuronidation activity against a variety of different structural types of substrates, but their activities were low. All six UGTs were successfully expressed and exhibited significantly improved glucuronidation activity when Trichopolusia ni cells BTI-TN5B1-4 (High Five) were used as the host. The recombinant human UGTs expressed in insect cells can catalyze the glucuronidation of their specific substrates, and the glucuronidation products were synthesized at milligram-scale with yields of 13%-66% for the first time, of which the structures were identified via MS, ¹H NMR, and ¹³C NMR spectroscopic analysis. Above all, the recombinant human UGTs yeast and insect cell expression systems constructed in this study can be used for in vitro metabolism evaluation in the early stage of new drugs research and development, and also provide a new tool for the synthesis of glucuronide metabolites.

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for non-invasive epidermal growth factor receptor mutations (EGFRm) detection in lung cancer patients, but existing methods have limitations in sensitivity and availability. In this study, we used the ΔCt value (mutant cycle threshold [Ct] value-internal control Ct value) generated during the polymerase chain reaction (PCR) assay to convert super-amplification-refractory mutation system (superARMS) from a qualitative method to a semi-quantitative method named reformed-superARMS (R-superARMS), and evaluated its performance in detecting EGFRm in plasma ctDNA in patients with advanced lung adenocarcinoma. METHODS: A total of 41 pairs of tissues and plasma samples were obtained from lung adenocarcinoma patients who had known EGFRm in tumor tissue and were previously untreated. EGFRm in ctDNA was identified by using superARMS. Through making use of ΔCt value generated during the detection process of superARMS, we indirectly transform this qualitative detection method into a semi-quantitative PCR detection method, named R-superARMS. Both qualitative and quantitative analyses of the data were performed. Kaplan-Meier analysis was performed to estimate the progression-free survival (PFS) and overall survival (OS). Fisher exact test was used for categorical variables. RESULTS: The concordance rate of EGFRm in tumor tissues and matched plasma samples was 68.3% (28/41). At baseline, EGFRm-positive patients were divided into two groups according to the cut-off ΔCt value of EGFRm set at 8.11. A significant difference in the median OS (mOS) between the two groups was observed (EGFRm ΔCt ≤8.11 vs. >8.11: not reached vs. 11.0 months; log-rank P = 0.024). Patients were divided into mutation clearance (MC) group and mutation incomplete clearance (MIC) group according to whether the ΔCt value of EGFRm test turned negative after 1 month of treatment. We found that there was also a significant difference in mOS (not reached vs. 10.4 months; log-rank P = 0.021) between MC group and MIC group. Although there was no significant difference in PFS between the two groups, the two curves were separated and the PFS of MC group tended to be higher than the MIC group (not reached vs. 27.5 months; log-rank P = 0.088). Furthermore, EGFRm-positive patients were divided into two groups according to the cut-off of the changes in ΔCt value of EGFRm after 1 month of treatment, which was set at 4.89. A significant difference in the mOS between the two groups was observed (change value of ΔCt >4.89 vs. ≤4.89: not reached vs. 11.0 months; log-rank P = 0.014). CONCLUSIONS Detecting EGFRm in ctDNA using R-superARMS can identify patients who are more likely sensitive to targeted therapy, reflect the molecular load of patients, and predict the therapeutic efficacy and clinical outcomes of patients.
Adenocarcinoma of Lung/genetics* ; Circulating Tumor DNA/genetics* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/genetics* ; Mutation/genetics* ; Protein Kinase Inhibitors

The chemical consituents from Artabotrys hongkongensis were separated and purified by column chromatographies with silica gel, Sephadex LH-20, ODS and RP-HPLC. The structures of the isolated compounds were identified on the basis of physicochemical properties and spectroscopic analysis, as well as comparisons with the data reported in the literature. As a result, 16 sesquiterpenes were isolated and elucidated as blumenol A (1), 4, 5-dihydroblumenol A (2), (6R, 9S)-3-oxo-a-ionol (3), 3-hydroxy-β-ionone (4), dehydrovomifoliol (5), (3R, 6R, 7E) -3-hydroxy-4, 7-megastigmadien-9-one (6), sarmentol F (7), 10-oxo-isodauc-3-en-15-oic acid (8), fukinone (9), petasitolone (10), β-eudesmol (11), trans-3β-(1-hydroxy-1-methylethyl)- 8aβ-methyl-5-methylenedecalin-2-one (12), 10-hydroxyaristolan-9-one (13), aristol-8-en-1-one (14), aristolan-9-en-1-one (15), and aristolan-1, 9-diene (16). This is the first study on the chemical consituents of A. hongkongensis, and all compounds were isolated from the genus Artabotrys for the first time.

Background:Chronic kidney disease (CKD) with moderate-to-severe renal dysfunction usually exhibits an irreversible course,and available treatments for delaying the progression to end-stage renal disease are limited.This study aimed to assess the efficacy and safety of the traditional Chinese medicine,Niaoduqing particles,for delaying renal dysfunction in patients with stage 3b-4 CKD.Methods:The present study was a prospective,randomized,double-blind,placebo-controlled,multicenter clinical trial.From May 2013 to December 2013,300 CKD patients with an estimated glomerular filtration rate (eGFR) between 20 and 45 ml,min-1· 1.73 m-2,aged 18-70 years were recruited from 22 hospitals in 11 Chinese provinces.Patients were randomized in a 1∶1 ratio to either a test group,which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks,or a control group,which was administered a placebo using the same methods.The primary endpoints were changes in baseline serum creatinine (Scr) and eGFR after completion of treatment.The primary endpoints were analyzed using Student's t-test or Wilcoxon's rank-sum test.The present study reported results based on an intention-to-treat (ITT) analysis.Results:A total of 292 participants underwent the ITT analysis.At 24 weeks,the median (interquartile range) change in Scr was 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) μmol/L for the test and control groups,respectively (Z =2.642,P =0.008),and the median change in eGFR was-0.2 (-4.3-2.7) and-2.2 (-5.7-0.8) ml·min-1.1.73 m-2,respectively (Z =-2.408,P =0.016).There were no significant differences in adverse events between the groups.Conclusions:Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD.This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction.

OBJECTIVETo analyze retrospectively the therapeutic efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelomonocytic leukemia (CMML).

METHODSThe engraftment, graft versus host disease (GVHD), infection, relapse, and survival of 13 CMML patients received allo-HSCT were observed. The clinical outcome of allo-HSCT for CMML was analyzed.

RESULTSThirteen (10 males and 3 females) CMML patients with a median age of 38 years old received allo-HSCT including 4 from HLA-matched unrelated donors, 6 from HLA-matched sibling donors and 3 from haploidentical related donors. All 13 patients achieved engraftment, and the median time of neutrophil engraftment and platelet engraftment were 12 (11-18) days and 15 (10-55) days respectively, acute GVHD occurred in 8 patients. After the median follow-up of 13 (6-29) months, the overall survival, disease free survival and relapse were 53.8%, 53.8%, 7.7%, respectively.

CONCLUSIONAllo-HSCT can improve the survival of patients with CMML, and is a effective method for treatment of CMML.

Adult ; Disease-Free Survival ; Female ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myelomonocytic, Chronic ; Male ; Retrospective Studies ; Siblings ; Tissue Donors ; Transplantation, Homologous

AIM: In an effort to identify novel, small molecules which can affect the proliferation of lung cancer cells, F-01A, a polyether antibiotic isolated from the fermentation broth of Streptomyces was tested. METHOD: F-01A was tested for its antitumor properties on the lung cancer cell line SPC-A-1, at six doses (0.1, 0.5, 1, 2.5, and 5 μmol·L(-1)), using various cellular assays. Cell viability was measured by the MTT assay, Hochest 33258 was used to study nuclear morphology; DNA ladder and the loss of mitochondrial membrane potential were also evaluated. RESULTS: F-01A induces apoptosis against SPC-A-1 cells in a dose-dependent manner. The IC50 is 0.65 μmol·L(-1), and the inhibition at 5 μmol·L(-1) is 87.89%. Further, JC-1 staining indicates F-01A could induce the loss of mitochondrial membrane potential, and the DNA fragment is evident. CONCLUSION Mechanistic analysis showed that F-01A induced apoptosis of cancer cells probably in the mitochondrial pathway. The antitumor actions of F-01A involve activation of the apoptotic pathway against SPC-A-1 cells, and it may be valuable for further drug development.
Anti-Bacterial Agents ; metabolism ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Growth Inhibitors ; pharmacology ; Humans ; Lung Neoplasms ; physiopathology ; Membrane Potential, Mitochondrial ; drug effects ; Streptomyces ; chemistry ; metabolism

OBJECTIVETo explore the better therapy for chronic tension-type headache (CTTH).

METHODSTwo hundred and eighty-eight cases were randomized into a sticking needling group (150 cases) and an acupuncture group (138 cases). In the sticking needling group, the manual sticking needling technique was adopted to stimulate the galea tendon-muscle node. In the acupuncture group, the conventional acupuncture therapy was applied to Baihui (GV 20), Sishencong (EX-HN 1), Fengchi (GB 20), Taiyang (EX-HN 5), Touwei (ST 18), Hegu (LI 4), etc. The treatment was given once a day, and 30 days made one session. After two sessions of treatment and after three months follow-up, CTTH score (including the score of headache attack frequency and the score of headache severity) was observed and compared before and after treatment separately. The efficacy was evaluated in two groups.

RESULTSCTTH score was all reduced after treatment in the two groups (both P<0.01), the score in the sticking needling group was lower than that in the acupuncture group (2.38 +/- 1.22 vs 4.16 +/- 2.54, P < 0.01). The effective rate was 97.3% (146/150) in the sticking needling group, which was better than 88.4% (122/138) in the acupuncture group (P < 0.05).

CONCLUSIONThe manual sticking needling technique at galea tendon-muscle node achieves the superior results of reducing the pain attack frequency and severity of CTTH as compared with the acupuncture therapy of the routine acupoint selection.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Female ; Humans ; Male ; Middle Aged ; Muscles ; physiopathology ; Tendons ; physiopathology ; Tension-Type Headache ; physiopathology ; therapy ; Treatment Outcome

OBJECTIVETo observe therapeutic effects of different acupuncture methods for recovery of mimetic function in the patient of spontaneous facial paralysis.

METHODSOne hundred and thirty-four cases of facial paralysis were randomly divided into a mimetic muscle acupuncture group (mimetic muscle group, n = 79) and a routine acupoint group (n = 55). The mimetic muscle group were treated by encircling needling frontal belly of epicranial muscle, orbicular muscle of eye, orbicular muscle of mouth and buccinator muscle, and the routine acupoint group with acupuncture at Dicang (ST 4), Jiache (ST 6), Yangbai (GB 14), Sibai (ST 2), Cuanzhu (BL 2), etc. on the affected side. Their therapeutic effects were compared after they were treated for 2 courses.

RESULTSThe effective rate and the good rate were 94.9% and 92.4% in the mimetic muscle group and 70.9% and 52.7% in the routine acupoint group, respectively, with a significant difference between the two groups (P < 0.05).

CONCLUSIONThe therapeutic effect of needling the mimetic muscle on spontaneous facial paralysis is superior to that of the routine acupuncture therapy.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Aged ; Facial Muscles ; physiopathology ; Facial Paralysis ; physiopathology ; therapy ; Female ; Humans ; Male ; Middle Aged ; Young Adult

OBJECTIVETo investigate the alkaloids from the stem of Artabotrys hainanensis.

METHODCompounds in plant extracts were separated by silica gel and sephadex LH-20 column chromatography. Chemical structures were elucidated by chemical and spectral analyses including UV, 1H-NMR, 13C-NMR, ESIMS and ESI-MS-MS.

RESULTEight alkaloids were isolated and identified as spinosine (1), 3-hydroxynornuciferine (2), juzirine (3), artabotrine (4), liridine (5), assimilobine (6), isococlaurine (7), N-demethylarmepavine (8).

CONCLUSIONAll alkaloids were isolated from this plant for the first time and compounds 1, 3, 7 and 8 were isolated from genus Artabotrys for the first time.

Alkaloids ; chemistry ; isolation & purification ; Annonaceae ; chemistry ; Berberine Alkaloids ; chemistry ; isolation & purification ; Isoquinolines ; chemistry ; isolation & purification ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Plants, Medicinal ; chemistry