Bioactive enmein-type 6,7-seco-ent-kaurane diterpenoids: natural products, synthetic derivatives and apoptosis related mechanism

Haonan Li,Baojia Sun,Mingying Wang,Xu Hu,Xiang Gao,Sheng-tao Xu,Yongnan Xu,Jin-yi Xu,Hui-Ming Hua,Da-Hong Li 대한약학회 2018 Archives of Pharmacal Research Vol.41 No.11

Diterpenoids are important and widely distributed natural compounds with various biological effects, including antitumor, anti-inflammatory and so on. Great efforts have been put in phytochemistry research on diterpenoids. A number of structural modified derivatives and pharmacophore incorporated hybrids were also designed and synthesized with promising therapeutic effects. Among the hopefuls, enmein-type 6,7-seco-ent-kaurane diterpenoids with unique ring system and stereogenic centers exhibit attractive activities. Based on their lead-like properties, enmein-type diterpenoids are suitable for further medicinal study. The derivatives were biologically evaluated and showed promising activities, which warranted in-depth research for further understanding. In this review, the natural bioactive enmein-type diterpenoids and the synthetic derivatives were comprehensively summarized.

Isochaetomium $A_2$, a new bis(naphthodihydropyran-4-one) with antimicrobial and immunological activities from fungus Chaetomium microcephalum

Xu, Guo-Bo,Yang, Tao,Bao, Jin-Ku,Fang, Dong-Mei,Li, Guo-You 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.5

Isochaetomium $A_2$ (1), a new bis(naphthodihydropyran-4-one), along with chaetochromins A (2) and B (3), was isolated from the solid-state fermented rice culture of Chaetomium microcephalum. The structure of compound 1 was elucidated on the basis of 1D and 2D NMR spectral data, and the relative configuration was confirmed by CD spectrum. Compounds 1-3 possessed significant antimicrobial activity against Escherichia coli 1.044, Staphylococcus aureus 1.252, and Bacillus subtilis 1.079. Moreover, compounds 1-3 showed obvious inhibitory effects on mouse spleen cell proliferation with successive $IC_{50}$ values of 0.52, 0.19, and $0.24{\mu}M$.

A Novel Monoclonal Antibody Induces Cancer Cell Apoptosis and Enhances the Activity of Chemotherapeutic Drugs

Xu, Heng,Tian, Yan-Na,Dun, Bo-Ying,Liu, Hai-Tao,Dong, Guang-Kuo,Wang, Jin-Hua,Lu, Shang-Su,Chen, Bo,She, Jin-Xiong Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

A novel monoclonal antibody (mAb), known as AC10364, was identified from an antibody library generated by immunization of mice with human carcinoma cells. The mAb recognized proteins in lysates from multiple carcinoma cell lines. Cell cytotoxicity assays showed that AC10364 significantly inhibited cell growth and induced apoptosis in multiple carcinoma cell lines, including Bel/fu, KATO-III and A2780. Compared with mAb AC10364 or chemotherapeutic drugs alone, the combination of mAb AC10364 with chemotherapeutic drugs demonstrated enhanced growth inhibitory effects on carcinoma cells. These results suggest that mAb AC10364 is a promising candidate for cancer therapy.

CHRNA5 rs16969968 Polymorphism Association with Risk of Lung Cancer - Evidence from 17,962 Lung Cancer Cases and 77,216 Control Subjects

Xu, Zhi-Wei,Wang, Guan-Nan,Dong, Zhou-Zhou,Li, Tao-Hong,Cao, Chao,Jin, Yu-Hong Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: Genetic studies have shown a possible relationship between the rs16969968 polymorphism in CHRNA5 and the risk of lung cancer. However, the results have been conflicting. Thus we rigorously conducted a meta-analysis to clarify any association. Materials and Methods: A total of 10 case-control studies involving 17,962 lung cancer cases and 77,216 control subjects were analysed. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of the association. Results: We found the CHRNA5 rs16969968 polymorphism to be associated with the risk of lung cancer (AA vs GG: OR=1.60, 95%CI=1.51-1.71). On stratified analysis by smoking status, a statistically significant increased risk was observed in the smoking group (AA vs GG: OR=1.80, 95%CI=1.61-2.01). However, this polymorphism was not associated with lung cancer risk in Asians (AA vs GG: OR=0.95, 95%CI=0.35-2.59), whereas it was linked to increased risk of lung cancer among Caucasians (AA vs GG: OR=1.65, 95%CI=1.55-1.76). Conclusions: Our meta-analysis provided statistical evidence for a strong association between rs16969968 polymorphism and the risk of lung cancer, especially in smokers and Caucasians. Application of this relationship may contribute to identification of individuals at high risk of lung cancer and indicate a chemoprevention target.

Construction of Modified Bacillus thuringiensis cry1Ac Genes for Transgenic Crop Through Multi Site-directed Mutagenesis

Xu, Hong Guang,Roh, Jong-Yul,Wang, Yong,Choi, Jae-Young,Shim, Hee-Jin,Liu, Qin,Tao, Xueying,Woo, Soo-Dong,Jin, Byung-Rae,Je, Yeon-Ho Korean Society of Sericultural Science 2009 International Journal of Industrial Entomology Vol.19 No.1

The newly cloned Bacillus thuringiensis cry1-5 gene showed high activity to both Plutella xylostella and Spodoptera exigua, while cry1Ac only showed high activity against P. xylostella but low to S. exigua. Through the alignment of amino acid sequences between Cry1Ac and Cry1-5, we found 12 different residues in domain I (6 residues) and domain II (6 residues). In this study, the modified cry1Ac gene, which is constructed according to a crop-preferring codon usage, was used as a template to construct mutant B. thuringiensis cry1Ac genes based on cry1-5 gene through multi site-directed mutagenesis. Total 63 various mutant cry genes were obtained at 12 positions randomly. Among them, ten mutant cry genes, whose domain I was totally converted and domain II was randomly, were selected to express in baculovirus expression system as a polyhedrin fusion form. The recombinant proteins were 95 kDa in size and were stably activated as 65 kDa by trypsin. The expressed mutant Cry proteins were applied to bioassays against P. xylostella and S. exigua. All mutants showed high insecticidal activity both to P. xylostella and S. exigua similar to cry1-5. These results suggest that these mutant cry genes might be expected of desirable cry genes for introduction to transgenic crops.

The Arabidopsis homolog of human minor spliceosomal protein U11-48K plays a crucial role in U12 intron splicing and plant development

Xu, Tao,Kim, Bo Mi,Kwak, Kyung Jin,Jung, Hyun Ju,Kang, Hunseung Oxford University Press 2016 Journal of experimental botany Vol.67 No.11

<P>The minor U12 introns are removed from precursor mRNAs by the U12 intron-specific minor spliceosome. Among the seven ribonucleoproteins unique to the minor spliceosome, denoted as U11/U12-20K, U11/U12-25K, U11/U12-31K, U11/U12-65K, U11-35K, U11-48K, and U11-59K, the roles of only U11/U12-31K and U11/U12-65K have been demonstrated in U12 intron splicing and plant development. Here, the functional role of the Arabidopsis homolog of human U11-48K in U12 intron splicing and the development of <I>Arabidopsis thaliana</I> was examined using transgenic knockdown plants. The <I>u11-48k</I> mutants exhibited several defects in growth and development, such as severely arrested primary inflorescence stems, formation of serrated leaves, production of many rosette leaves after bolting, and delayed senescence. The splicing of most U12 introns analyzed was impaired in the <I>u11-48k</I> mutants. Comparative analysis of the splicing defects and phenotypes among the <I>u11/u12-31k</I>, <I>u11-48k</I>, and <I>u11/12-65k</I> mutants showed that the severity of abnormal development was closely correlated with the degree of impairment in U12 intron splicing. Taken together, these results provide compelling evidence that the Arabidopsis homolog of human U11-48K protein, as well as U11/U12-31K and U11/U12-65K proteins, is necessary for correct splicing of U12 introns and normal plant growth and development.</P>

Genome-wide identification and characterization of the Dof gene family in moso bamboo (Phyllostachys heterocycla var. pubescens)

Tao Wang,Jin-Jun Yue,Xue-Ji Wang,Lu Xu,Lu-Bin Li,Xiao-Ping Gu 한국유전학회 2016 Genes & Genomics Vol.38 No.8

The Dof (DNA binding with One Finger) family of single zinc finger proteins is a family of plant-specific transcription factors. These transcription factors have a variety of important functions in different biological processes in plants. In the current study, we identified 26 Dof family genes in moso bamboo (Phyllostachys heterocycla var. pubescens). A complete overview of PhDof genes in moso bamboo is presented, including the gene structures, phylogeny, protein motifs and expression patterns. Phylogenetic analysis of the 26 PhDof proteins identified four classes constituting seven clusters (A, B1, C1, C2, D1, D2 and D3). In addition, a comparative analysis between the Dof genes in moso bamboo, Arabidopsis (Arabidopsis thaliana L.) and rice (Oryza sativa L.) was also performed, and several putative paralogous and orthologous genes were identified. The exon numbers in Dof genes ranged from one to three in many plants; however, the exon number in PhDofs ranged from one to four. The PhDof genes displayed differential expression in different parts of the shoot and at different flower development stages. This study represents the first step towards a genome-wide analysis of the Dof genes in moso bamboo. Our study provides a useful reference for cloning and functional analysis of members of the Dof gene family in moso bamboo and other species.

A Novel In Situ Gel Formulation of Ranitidine for Oral Sustained Delivery

( Tao Ma ),( Hao Ping Xu ),( Min Shi ),( Jin Ling Jiang ) 한국응용약물학회 2014 Biomolecules & Therapeutics(구 응용약물학회지) Vol.22 No.2

The main purpose of this study was to develop a novel, in situ gel system for sustained delivery of ranitidine hydrochloride. Ranitidinein situ gels at 0.2%, 0.5%, and 1.0% gellan gum concentration (w/v) were prepared, respectively, and characterized in termsof preparation, viscosity and in vitro release. The viscosity of the gellan gum formulations in solution increased with increasingconcentrations of gellan gum. In vitro study showed that the release of ranitidine from these gels was characterized by an initialphase of high release (burst effect) and translated to the second phase of moderate release. Single photon emission computingtomography technique was used to evaluate the stomach residence time of gel containing 99mTc tracer. The animal experimentsuggested in situ gel had feasibility of forming gels in stomach and sustained the ranitidine release from the gels over the periodof at least 8 h. In conclusion, the in situ gel system is a promising approach for the oral delivery of ranitidine for the therapeuticeffects improvement.

Preliminary Results for the Treatment of a Pain-Causing Osteoporotic Vertebral Compression Fracture with a Sky Bone Expander

Jin-bo Liu,Xue-ming Tang,Nan-wei Xu,Hong-tao Bao 대한영상의학회 2008 Korean Journal of Radiology Vol.9 No.5

Objective: Vertebral compression fractures (VCFs) are common complications of osteoporosis. The expansion of VCFs with a Sky Bone Expander is a new procedure which improves kyphotic deformities and decreases pain associated with VCFs. The purpose of this study was to investigate the preliminary results for the treatment of painful osteoporotic VCFs with a Sky Bone Expander. Materials and Methods: Twenty-six patients with pain-causing VCFs were treated with a Sky Bone Expander. This operation involved the percutaneous insertion of the Sky Bone Expander into a fractured vertebral body transpedicularly. Following the expansion, the Sky Bone Expander was contracted and removed, resulting in a cavity to be filled with bone cement. All fractures were analyzed for improvement in sagittal alignment. Clinical complications, pain relief and ambulation status were evaluated 1 day, 1 week, 1 month, and 3 months after the operation. Results: Twenty-four hours after the operation, all the patients treated experienced some degree of pain relief. In addition, no postoperative neurologic complications were noted. The average operative time was 42.4 ± 15.5 min per vertebra. Moreover, an average cement volume of 3.5 mL (range, 2.5 ± 5.0 mL) was injected per vertebra. The average anterior height was 18.4 ± 5.1 mm preoperatively and 20.5 ± 5.3 mm postoperatively (p < 0.01). Furthermore, the average midline height was 15.5 ± 5.2 mm preoperatively and 18.9 ± 4.0 mm postoperatively (p < 0.01). The Cobb angle improved from 18.5 ± 8.2 degrees preoperatively to 9.2 ± 4.0 degrees postoperatively (p < 0.01). The Visual Anabog Scale scores decreased from 7.7 ± 1.8 points preoperatively to 3.1 ± 2.0, 2.9 ± 1.7, 2.6 ± 1.5 and 2.9 ± 11.3 after 1 day, 1 week, 1 month and 3 months after the operation, respectively. Cement extrusion was observed in four patients without any neurologic symptoms. Conclusion: As a result of this study, we can postulate that the expansion of compressed vetrebra with a Sky Bone Expander is a safe and minimally invasive procedure resulting in the restoration of vertebral body height and the relief of pain associated with VCFs. Objective: Vertebral compression fractures (VCFs) are common complications of osteoporosis. The expansion of VCFs with a Sky Bone Expander is a new procedure which improves kyphotic deformities and decreases pain associated with VCFs. The purpose of this study was to investigate the preliminary results for the treatment of painful osteoporotic VCFs with a Sky Bone Expander. Materials and Methods: Twenty-six patients with pain-causing VCFs were treated with a Sky Bone Expander. This operation involved the percutaneous insertion of the Sky Bone Expander into a fractured vertebral body transpedicularly. Following the expansion, the Sky Bone Expander was contracted and removed, resulting in a cavity to be filled with bone cement. All fractures were analyzed for improvement in sagittal alignment. Clinical complications, pain relief and ambulation status were evaluated 1 day, 1 week, 1 month, and 3 months after the operation. Results: Twenty-four hours after the operation, all the patients treated experienced some degree of pain relief. In addition, no postoperative neurologic complications were noted. The average operative time was 42.4 ± 15.5 min per vertebra. Moreover, an average cement volume of 3.5 mL (range, 2.5 ± 5.0 mL) was injected per vertebra. The average anterior height was 18.4 ± 5.1 mm preoperatively and 20.5 ± 5.3 mm postoperatively (p < 0.01). Furthermore, the average midline height was 15.5 ± 5.2 mm preoperatively and 18.9 ± 4.0 mm postoperatively (p < 0.01). The Cobb angle improved from 18.5 ± 8.2 degrees preoperatively to 9.2 ± 4.0 degrees postoperatively (p < 0.01). The Visual Anabog Scale scores decreased from 7.7 ± 1.8 points preoperatively to 3.1 ± 2.0, 2.9 ± 1.7, 2.6 ± 1.5 and 2.9 ± 11.3 after 1 day, 1 week, 1 month and 3 months after the operation, respectively. Cement extrusion was observed in four patients without any neurologic symptoms. Conclusion: As a result of this study, we can postulate that the expansion of compressed vetrebra with a Sky Bone Expander is a safe and minimally invasive procedure resulting in the restoration of vertebral body height and the relief of pain associated with VCFs.

Comparison Different Methods of Intraoperative and Intraperitoneal Chemotherapy for Patients with Gastric Cancer: A Meta-analysis

Huang, Jin-Yu,Xu, Ying-Ying,Sun, Zhe,Zhu, Zhi,Song, Yong-Xi,Guo, Peng-Tao,You, Yi,Xu, Hui-Mian Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.9

Purpose: To investigate the efficacy and safety of intraperitoneal chemotherapy (IPC) for patients with gastric cancer and to compare effects between different regimens of IPC. Method: Randomized controlled trials comparing the effects of surgery plus intraperitoneal chemotherapy with surgery alone or comparing the efficacy between different regimens of intraperitoneal chemotherapy were searched for in Medline, Embase, Pubmed, the Cochrane Library and the Chinese BioMedical Disc and so on by two independent reviewers. After quality assessment and data extraction, data were pooled for meta-analysis using RevMan5.16 software. Tests of interaction were used to test for differences of effects among subgroups grouped according to different IPC regimens. Results: Fifteen RCTs with a total of 1713 patients with gastric cancer were included for quality assessment and data extraction. Ten studies were judged to be of fair quality and entered into meta-analysis. Hyperthermic intraoperative intraperitoneal chemotherapy (HR=0.60, P<0.01), hyperthermic intraoperative intraperitoneal chemotherapy plus postoperative intraperitoneal chemotherapy (HR=0.47, P<0.01) and normothermic intraoperative intraperitoneal chemotherapy (HR=0.70, P=0.01) were associated with a significant improvement in overall survival. Tests of interaction showed that hyperthermia and additional postoperative intraperitoneal chemotherapy did not impact on its effect. Further analysis revealed that intraperitoneal chemotherapy remarkably decrease the rate of postoperative hepatic metastasis by 73% (OR=0.27, 95% CI=0.12 to 0.67, P<0.01). However, intraperitoneal chemotherapy increased risks of marrow depression (OR=5.74, P<0.01), fever (OR=3.67, P=0.02) and intra-abdominal abscess (OR=3.57, P<0.01). Conclusion: The present meta-analysis demonstrates that hyperthermic intraoperative intraperitoneal chemotherapy and normothermic intraoperative intraperitoneal chemotherapy should be recommended to treat patients with gastric cancer because of improvement in overall survival. However, it is noteworthy that intraperitoneal chemotherapy can increase the risks of marrow depression, intra-abdominal abscesses, and fever.