Sixteen compounds were isolated from the aerial parts of Euphorbia sikkimensis by means of various chromatographic techniques such as silica gel, Sephades LH-20 and RP-18, and their structures were elucidated as naringenin (1), kaempferol (2), quercetin (3), kaempferol-3-O-alpha-L-arabinopyranoside (4), quercetin-3-O-alpha-L-arabinopyranoside (5), quercetin-3-O-(2"-galloyl)-alpha-L-arabinopyranoside (6), 5alpha, 8alpha-epidioxy-(22E, 24R)-ergosta-6,22-dien-3beta-ol (7), stigmast-5-ene-7-one-3beta-ol (8), 3beta-hydroxy4a, 14alpha-dimethyl-5alpha-ergosta-8, 24(28)-dien-7-one(9), beta-sitosterol (10) , 10-cucurbitadienol( 1) , scopoletin(12) , ethyl gallate(13), p-hydroxybenzaldehyde (14), 3 betahydroxybenzeneethanol( 15) ,and 2,4-dihydroxy-6-methoxy-acetophenone (16) on the basis of spectroscopic data analysis. All the compounds are isolated from this plant for the first time, and compounds 1, 4-8, 15 are obtained from Euphorbia species for the first time.
Chromatography ; Euphorbia ; chemistry ; Organic Chemicals ; analysis ; isolation & purification

Apoptosis is an essential factor in keeping homeostasis of the organism. Apoptosis is regulated by a series of cytokines. Bcl-2 family proteins are key regulators of apoptosis. The Bcl-2 family includes both anti- and pro-apoptotic proteins with opposing biological functions. Their interaction regulates the transmission of the apoptosis signal. High expression of anti-apoptotic members such as Bcl-2 and Bcl-xL are commonly found in human cancers. In recent years, following the disclosing of the crystal structures of Bcl-2 family proteins, researchers have paid attention to the development of the small molecule inhibitors of Bcl-2 family proteins. This article reviews the progress in this field from the view of drug design.
Antimycin A ; chemistry ; pharmacology ; Antineoplastic Agents ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Benzopyrans ; chemistry ; pharmacology ; Biphenyl Compounds ; chemistry ; pharmacology ; Cell Line, Tumor ; Drug Design ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Gossypol ; chemistry ; pharmacology ; Humans ; Nitriles ; chemistry ; pharmacology ; Nitrophenols ; chemistry ; pharmacology ; Piperazines ; chemistry ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; antagonists & inhibitors ; pharmacology ; Structure-Activity Relationship ; Sulfonamides ; chemistry ; pharmacology ; Thiazoles ; chemistry ; pharmacology ; bcl-X Protein ; antagonists & inhibitors ; pharmacology

Animals ; Cochlea ; pathology ; ultrastructure ; Diabetes Mellitus, Experimental ; pathology ; Male ; Mitochondria ; pathology ; ultrastructure ; Rats ; Rats, Sprague-Dawley

Chinese materia medica resource (CMM resource) is the foundation of the development of traditional Chinese medicine. In the study of sustainable utilization of CMM resource, adopting innovative theory and method to find new CMM resource is one of hotspots and always highlighted. Pharmacophylogeny interrogates the phylogenetic relationship of medicinal organisms (especially medicinal plants), as well as the intrinsic correlation of morphological taxonomy, molecular phylogeny, chemical constituents, and therapeutic efficacy (ethnopharmacology and pharmacological activity). This new discipline may have the power to change the way we utilize medicinal plant resources and develop plant-based drugs. Phylogenomics is the crossing of evolutionary biology and genomics, in which genome data are utilized for evolutionary reconstructions. Phylogenomics can be integrated into the flow chart of drug discovery and development, and extends the field of pharmacophylogeny at the omic level, thus the concept of pharmacophylogenomics could be redefined in the context of plant pharmaceutical resources. This contribution gives a brief discourse of knowledge pedigree of pharmacophylogeny, epistemology and paradigm shift, highlighting the theoretical and practical values of pharmacophylogenomics. Many medicinally important tribes and genera, such as Clematis, Pulsatilla, Anemone, Cimicifugeae, Nigella, Delphinieae, Adonideae, Aquilegia, Thalictrum, and Coptis, belong to Ranunculaceae family. Compared to other plant families, Ranunculaceae has the most species that are recorded in China Pharmacopoeia (CP) 2010. However, many Ranunculaceae species, e. g., those that are closely related to CP species, as well as those endemic to China, have not been investigated in depth, and their phylogenetic relationship and potential in medicinal use remain elusive. As such, it is proposed to select Ranunculaceae to exemplify the utility of pharmacophylogenomics and to elaborate the new concept empirically. It is argued that phylogenetic and evolutionary relationship of medicinally important tribes and genera within Ranunculaceae could be elucidated at the genomic, transcriptomic, and metabolomic levels, from which the intrinsic correlation between medicinal plant genotype and metabolic phenotype, and between genetic diversity and chemodivesity of closely related taxa, could be revealed. This proof-of-concept study regards pharmacophylogenomics as the updated version of pharmacophylogeny and would enrich the intension and spread the extension of pharmacophylogeny. The interdisciplinary knowledge and techniques will be integrated in the proposed study to promote development of CMM resource discipline and to boost sustainable development of Chinese medicinal plant resources.
China ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Knowledge ; Medicine, Chinese Traditional ; Phylogeny ; Plants, Medicinal ; chemistry ; classification ; genetics

The inhibition of protein degradation through the ubiquitin-proteasome pathway is a recently developed approach to cancer treatment which extends the range of cellular target for chemotherapy. This therapeutic strategy is very interesting since the proteasomes carry out the regulated degradation of unnecessary or damaged cellular proteins, a process that is dysregulated in many cancer cells. Based on this hypothesis, the proteasome complex inhibitor Bortezomib was approved for use in multiple myeloma patients by FDA in 2003. Drug discovery programs in academy and the pharmaceutical industry have developed a range of synthetic and natural inhibitors of the 20S proteasome core particle that have entered human clinical trials as significant anti-cancer leads. The main results from the use of proteasome inhibition in cancer chemotherapy, the structure of several proteasome inhibitors and their synthesis is going to be reviewed in this paper.
Acetylcysteine ; analogs & derivatives ; chemical synthesis ; chemistry ; Antineoplastic Agents ; chemical synthesis ; classification ; therapeutic use ; Boronic Acids ; chemical synthesis ; chemistry ; therapeutic use ; Bortezomib ; Cysteine Proteinase Inhibitors ; chemical synthesis ; classification ; Dipeptides ; chemical synthesis ; chemistry ; Humans ; Multiple Myeloma ; drug therapy ; enzymology ; Peptides, Cyclic ; chemical synthesis ; chemistry ; Proteasome Endopeptidase Complex ; metabolism ; Proteasome Inhibitors ; Pyrazines ; chemical synthesis ; chemistry ; therapeutic use ; Ubiquitin ; antagonists & inhibitors ; metabolism

Bacillus anthracis collagen-like protein(BclA) is a structural component of the exosporium filaments,as well as the immunodominant antigen on the spore surface.The genes encoding BclA proteins were cloned and sequenced from three Bacillus anthracis strains separated from China.It was founded that the BclA proteins of strain A16R and 40048,containing 388 and 322 amino acids,72 and 50 copies of GXX repeat,5 and 3 copies of 21-amino-acid sequence(GPT)_(5)GDTGTT(BclA repeat) respectively,are different from those reported by foreign scholars;while the BclA protein of strain 40022,containing 370 amino acids,66 copies of GXX repeat,and 5 copies of BclA repeat,is identical with that of strain 53169 reported by others.The results are helpful for the molecular typing of B.anthracis strains,and provide a basis for the elucidation of the pathogenesis and immunogenicity of B.anthracis spore.

Objective To investigate the therapeutic effect and adverse effects of the teniposide-based regimen in patients with primary central nervous system lymphoma (PCNSL). Methods Between March 2011 and July 2013, 16 patients with PCNSL were diagnosed and treated. The clinical characteristics, diagnosis,therapy, results and adverse effects were analyzed. Results Totally 16 patients were enrolled and diagnosed as primary central nervous system diffuse large B-cell lymphoma. All patients received teniposide-based regimen chemotherapy and 9 patients received teniposide plus rituximab. The overall response rate was 87.5 % (14/16), including 10 cases of CR and 4 cases of PR. With a median follow-up of 13.5 months, the progression-free survival (PFS) and overall survival (OS) rates of 2 years were 29.9 % and 66.7 %, respectively. The mainly hematological adverse events were neutropenia, including grade 3 in 4 cases (25 %) and grade 4 just in one case. There was one case of treatment related death. Conclusions The response rate of teniposide-based regimen for PCNSL is promising. The 2 year PFS and OS rates are even higher than results of traditional high-dose methotrexate regimen. The teniposide-based regimen is well tolerated, and the adverse events are acceptable.

Objective To analyze the clinical characteristics , diagnosis, therapy and prognosis of new diagnosed pri-mary gastric diffuse large B cell lymphoma ( PGDLBCL) and to discuss the efficacy of rituximab .Methods Between Jan 2005 and May 2012 , twenty-six new-diagnosed PGDLBCL patients were reviewed retrospectively .The clinical characteris-tics, diagnosis, therapy, results and prognostic factors were analyzed .Results There were 14 males and 12 females.Their age ranged from 25 to 82 (median, 50.1) years old.The most common symptom was stomachache .Treatment strategies were chemotherapy alone ( n=9) [ scheduled as cyclophosphamide , doxorubicin , vincristine and prednisone ( CHOP) and CHOP-like] and chemotherapy combined with rituximab (n=17), followed by radiotherapy of the stomach with or without regional nodes .All clinical and pathological features were similar between the two groups .The median follow-up time was 40 months.The overall response rate was 100%(9/9)in CHOP group, including 55.56%(5/9) CR, and 93.75%(15/16) in RCHOP group including 50%(8/16) CR (P>0.05).The total PFS and OS of 5 years were 60.3%and 74.4%respectively.The PFS in CHOP group and RCHOP group was 66.7% and 58.9%, respectively,and the OS was 66.7%and 84.6%, respectively.Although the OS of RCHOP group was much better than that of CHOP group , there was no sta-tistically significant difference.Univariate analysis showed that IPI (P<0.05) and Lugano staging (P<0.05) were inde-pendent factors of survival in patients with PGDLBCL .Conclusion Chemotherapy could be the first-line therapy of PGDL-BCL.The overall survival rate might be increased by adding rituximab to chemotherapy .The Lugano stage and IPI are im-portant prognostic factors .

Objective To summarize the clinical characteristics and diagnosis and treatment of hemangioma of small intestine in children.Methods Location,pathology,clinical manifestation,diagnosis and treatment of 3 cases from our hospital and 44 cases reported in our courtry with hemangioma of the small bowel were analyzed from 1994 to 2004.Results These tumors locating in jejunum,ileum,duodenum as well as parts small intestine were 31.9%,42.6%,4.2% and 21.3%,respectively.Solitary and multiple tumors were 29.8% and 70.2% separately.The histopatholical report of 10 cases revealed that capillary,cavernous,mixed type hemangioma and hematolymphangioma were 2,6,1 and 1 cases,respectively.Thirty nine children presented with recurrent black stool.Five patients manifest in the form of intussusception.One child passed a bloody stool so massive as to cause shock.Small-bowel obstruction occurred in 5 cases.The hemoglobin of 38 patients were lower than 90 g/L.The incidence of preoperative diagnosis was only 10.6%.All of patients were performed operation.Conclusions The frequent locations of hemangioma of small intestine are in ileum and jejunum,and multiple tumors are common.The diseases are characterized as recurrent hematochezia with painlessness.Preoperative diagnosis of a small bowel hemangioma can be very difficult.The segments of small bowel with hemangioma resection are the most method of the treatment.

AIMTo investigate the impact of CYP2C9 * 3 on the pharmacokinetics of glibenclamide and lornoxicam.

METHODSCYP2C9 * 3 was measured in 83 non-related Chinese subjects by PCR-RFLP. The pharmacokinetics of lornoxicam and glibenclamide were investigated in 18 subjects (7 with CYP2C9 * 1/* 3 genotype and 11 with * 1/* 1 genotype). Glibenclamide and lornoxicam in plasma were determined by the sensitive liquid chromatography-tandem mass spectrometry, separately.

RESULTSAfter a single oral dose of 2.5 mg glibenclamide, C(max) was (70.0 +/- 11.5) microg x L(-1) in CYP2C9 * 1/ * 3 subjects and (51.9 +/- 12.3) microg x L(-1) in * 1/ *1 subjects. AUC(0-infinity) were (435 +/- 47) vs (287 +/- 95) microg x h x L(-1) (in * 1/ * 3 vs * 1/ *1 subjects), and CL/F were (96 +/- 9.3) vs (160 +/- 51) mL x min(-1), respectively. Statistic analysis results indicated that glibenclamide AUC(0-infinity) was significantly higher (1.5-fold) and subsequently CL/F was significantly lower (40%) in CYP2C9 * 1/ * 3 subjects than those in * 1/ * 1 subjects (P < 0.01). After a single oral dose of 8 mg lornoxicam, C(max) was (1.54 +/- 0.24) mg x L(-1) in CYP2C9 * 1/ * 3 subjects and (1.19 +/- 0.37) mg x L(-1) in * 1/ * 1 subjects. AUC(o-infinity were (14.9 +/- 2.2) vs (6.92 +/- 1.48) mg x h x L(-1) (in * 1/ *3 vs * 1/ * 1 subjects), and CL/F were (9.1 +/- 1.2) vs (20.1 +/- 4.6) mL x min(-1), respectively. Statistic analysis results indicated that lornoxicam AUC(0-infinity) was significantly higher (2. 2-fold) and subsequently CL/F was significantly lower (55% ) in CYP2C9 * 1/ * 3 subjects than those in * 1/ * 1 subjects (P < 0.001).

CONCLUSIONCYP2C9 * 3 greatly affects both the pharmacokinetic profiles of glibenclamide and lornoxicam. The elimination of these drugs significantly decreased in subjects with CYP2C9 * 1/ * 3 genotype, especially lornoxicam.

Adult ; Alleles ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacokinetics ; Area Under Curve ; Aryl Hydrocarbon Hydroxylases ; genetics ; Asian Continental Ancestry Group ; China ; Cytochrome P-450 CYP2C9 ; Genotype ; Glyburide ; pharmacokinetics ; Humans ; Hypoglycemic Agents ; pharmacokinetics ; Male ; Piroxicam ; analogs & derivatives ; pharmacokinetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length