Polyketides are very large group of natural products with functional and structural diversity.Most of them are produced by microor- ganism and have medicinal activities,including antibiotic,anticancer,antifungal and antiparasitic properties.The researchs in this area have progressed greatly.More and more polyketides are discovered,on the other hand the mechanisms of biosynthesis of those various polyketides are researched more deeply and clearly.The article reviewed the progress of the research in the diversity of polyketide synthases and the mechanisms of polyketide biosynthesise.

BACKGROUND:Whether determination of tacrolimus blood concentration by different immunoassay methods can influence predictive ability to immunosuppressive effects and toxicity, and whether it can be more sensitive to reflect blood concentration in patients with renal dysfunction are worthy of studying.
OBJECTIVE:To analyze the correlation of tacrolimus (FK506) concentrations determined by enzyme-multiplied immunoassay technique (EMIT) and enzyme linked immunosorbent assay (ELISA) in combination with renal function parameters.
METHODS:133 clinical blood samples were col ected. EMIT and ELISA techniques were used to determine the FK506 concentration. The correlation of two determination methods were analyzed, combined with renal function. RESULTS AND CONCLUSION:In patients with renal dysfunction, the mean results and standard deviation mensurated by ELISA were higher than those by EMIT. For blood concentration in 5-20μg/L by ELISA, the incidence of renal dysfunction occurred less than by EMIT. The overal mean results of blood concentration for two methods appeared no significant difference (r=0.904 5, P>0.05). When the concentration was less than 2.0μg/L, the concentration results by EMIT were higher than those by ELISA (P<0.01). When the concentration was more than 2.0μg/L, there was no significant difference between two determination methods (P>0.05). These findings indicate that EMIT and ELISA has good correlation, which are both suitable for clinical routine determination of plasma concentration. It is not recommended for applying EMIT method to determine low blood concentrations (<2.0μg/L). The reference range of concentration should be compartmentalized depending on combination of determination methods and renal function.

Aim To investigate the effect of DHA on NGF-induced neuronal differentiation of PC12 cells and explore the possible mechanism via regulating BMP pathway. Methods PC12 cells were treated with 100μg·L-1 NGF and 100 μg·L-1 NGF + 10 μmol· L-1 DHA for 3, 6 and 9 days respectively. The length and number of neurite were detected by immunofluores-cenc. DHA content was analyzed by gas chromatogra-phy in all groups. The protein expression of BMP4, BMP7 , BMPR-II and p-Smad 1/5/8 was determined by Western blot. Results The length of total primary neurite in NGF+DHA groups was obviously increased, longer than that in NGF group; DHA content in 10μmol · L-1 DHA group was higher than that in the control group;NGF+DHA groups also unregulated the protein expression of BMP4 , BMP7 , BMPR-II and p-Smad 1/5/8 . Conclusion DHA promotes NGF-in-duced neuronal differentiation in PC12 cells, which may be associated with the upregulation of BMP path-way protein.

Aim:To investigate the effect of Hemangiopoietin (HAPO) on the hematopoiesis reconstitution in sub-lethally irradiated Balb/c mice.Methods: Balb/c mice were underwent total body irradiation at 700 cGy 137Cs ? radiation and were treated with HAPO or recombinant human granulocyte colony stimulating factor (rhG-CSF) after irradiation. The hematopoiesis reconstitution of mice were detected. Cells from bone marrow of Balb/c mice were cultured with HAPO or rhG-CSF for 24 hours or 72 hours before or after the cells were irradiated. The viability of cells were assessed and the ability of in vitro hematopoiesis reconstitution were also detected. Result: rhG-CSF and HAPO treated mice both showed increased survival rate and increased colony forming units. The peripheral WBC number increased greatly. The HAPO group was most quickest compared with rhG-CSF group and PBS control group. The number of bone marrow cells at day 14 of rhG-CSF group was higher than that in HAPO group, but the number of bone marrow cells at day 32 of rhG-CSF was lower than that in HAPO group. The number of bone marrow cells at day 42 of rhG-CSF was below normal. The number of bone marrow cells at day 42 of HAPO group was nearly normal. The number of CFU-GEMM in HAPO group was most compared with that in rhG-CSF group and PBS control group at day 7, 14 and 21 after radiation. The survival rate of cells after radiation in HAPO group was markedly higher than that in PBS control group, but the survival rate of cells after radiation in rhG-CSF group was no notable difference compared with that in PBS control group. In MTT assay, both HAPO and rhG-CSF incubation stimulated proliferation of bone marrow cell at 72 hours after radiation. Bone marrow cells formed Hematopoietic islands in HAPO group after radiation and were positive for sca-1 and CD31. CD31 positive endothelial cells increased around the Hematopoietic islands. There was no Hematopoietic islands formation, few CD31 positive endothelial cells and no sca-1 positive cells in PBS control group. Conclusion: HAPO can promote hematopoiesis reconstitution in sub-lethally irradiated Balb/c mice. It can increase the survival rate of mice and stimulate the proliferation of hematopoietic stem cells.

Objective To investigate the effects of in situ venous arterialization on extensive artery obliterans occlusion of the lower extremity. Methods Lumbar sympathetic ganglionectomy and one stage in situ arterialization of the great saphemous vein were performed in 104 ischemic limbs of 88 patients with extensive arterial occlusion. Results Eighty-two of 104 limbs were followed-up from 6 months to over 6 years. The intermittent claudication, night pain improved in all cases, with satisfactory wound healing and no swelling of the lower limbs. Conclusions Arterial blood flow through venous conduit improves and reconstructs the blood circulation of the ischemic limbs.

OBJECTIVETo explore the correlation between Pi and Shen by observing the relationship between the metabolism of aristolochic acid (AA) and mRNA and protein expression levels of organic anion transporting polypeptide (oatp) superfamily member 2a1 and 2 b1 (oatp2al and oatp2bl) in renal, small intestinal, and large intestinal tissues of Pi deficiency syndrome (PDS) model rats.

METHODSTotally 46 Sprague-Dawley (SD) rats were randomly divided into four groups, i.e., the blank group (n = 12), the PDS group (n = 22), the AA-I group (n = 6), and the PDS AA-I group (n = 6). PDS model was established by subcutaneously injecting Reserpine at the daily dose of 5 mg/kg for 16 successive days. Carotid intubation was performed in 6 rats selected from the blank group and the PDS group. Pharmacokinetics of AA-I were detected at 5, 15, 30, 45, and 60 min after gastrogavage of AA-I. AA-I concentrations in renal, small intestinal, and large intestinal tissues of 10 rats selected from the PDS group were determined. Normal saline was administered to 6 rats selected from the PDS group and the blank group by gastrogavage. Renal, small intestinal, and large intestinal tissues were collected in the AA-I group and the PDS AA-I group at 60 min after gastrogavage of AA-I. mRNA and protein expression levels of oatp2a1 and oatp2b1 in each tissue were detected using real-time polymerase chain reaction (RT- PCR) and Western blot.

RESULTSCompared with the blank group, plasma concentrations of in vivo AA-I were obviously higher in the PDS group at 15, 30, 45, and 60 min after gastrogavage of AA-I with statistical difference (P < 0.05). Plasma concentrations of AA-I were obviously decreased at 60 min after gastrogavage of AA-I; AA-I concentrations in renal and large intestinal tissues were elevated; AA-I concentrations in small intestinal tissues were obviously reduced in the PDS group. There was no statistical difference in mRNA expression levels of oatp2a1 and oatp2b1 in the aforesaid three tissues of rats between the blank group and the PDS group. Compared with the blank group, mRNA expression levels of oatp2a1 and oatp2b1 decreased in small intestinal tissues of the AA-I group, and the mRNA expression level of oatp2a1 in large intestinal tissues significantly decreased (P < 0.05, P < 0.01). Compared with the PDS group, mRNA expression levels of oatp2a1 and oatp2b1 increased in renal tissues of the PDS AA-I group (P < 0.05); mRNA expression levels of oatp2b1 increased in large intestinal tissues of the PDS AA-I group (P < 0.05).

CONCLUSIONSThe difference in AA-I metabolism might be associated with changed expression levels of oatp2a1 and oatp2b1 in renal, small intestinal, and large intestinal tissues under Pi deficiency induced loss of transportation. Shen and Dachang played important roles in substance metabolism under Pi deficiency state, which proved Pi-Shen correlated in Chinese medical theories.

Animals ; Anions ; Aristolochic Acids ; metabolism ; Drugs, Chinese Herbal ; Kidney ; Medicine, Chinese Traditional ; Organic Cation Transport Proteins ; metabolism ; Peptides ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo analyze the relationship of K-ras mutation with the development of liver metastasis in colorectal cancer patients and the survival outcomes.

METHODSFrom 2003 to 2008, 300 patients who underwent colorectal cancer surgery in the Department of General Surgery of Zhongshan Hospital, Fudan University were assigned to different groups, according to the diagnosis and follow-up results. The mutation of exon 2 of K-ras was detected in primary paraffin-embedded lesions by PCR and Pyrosequencing. The association of gene mutation with the development of liver metastasis and its prognosis was studied.

RESULTSAmong 300 cases, the mutations of exon 2 were present in 120 cases(40%). The G13D mutation was more common in metachronous metastasis group than that in synchronous group(17.0% vs. 8.0%, P=0.041). Multivariable regression analysis showed that G13D mutation was an independent risk factor(HR=1.108, 95%CI:1.032-5.062, P=0.048) for metachronous metastasis. Patients with mutated K-ras had a poorer overall survival compared to those without mutated K-ras for patients without liver metastasis(median overall, 65 vs. 72 months, P=0.039), and for patients who received metastasis resection(median disease-free survival 18 vs. 24 months, P=0.048). Multivariable analysis showed that K-ras mutation was an independent risk factors of overall survival(HR=1.561, 95%CI:1.022-6.422, P=0.045) in patients without liver metastasis.

CONCLUSIONDetection of K-ras mutation may predict the development of liver metastasis and prognosis.

Aged ; Colorectal Neoplasms ; genetics ; pathology ; Female ; Genes, ras ; genetics ; Humans ; Liver Neoplasms ; genetics ; secondary ; Male ; Mutation ; Prognosis

Objective To analyze the clinical, imaging characteristics and NOTCH3 mutations of cerebral autosomal dominant arteriopathy with the subcortical infarcts and leukoencephalopathy (CADASIL) in Henan, China.Methods CADASIL patients diagnosed by gene or biopsy in People′s Hospital of Zhengzhou University between 2012-2016 were recruited.Clinical and imaging features of these patients were analyzed retrospectively.The distribution of NOTCH3 gene mutations hotspots was described in Henan region at the same time.Results There were 37 patients from 19 families who were diagnosed as CADASIL by genetic testing or biopsy, 27 of whom had symptoms of CADASIL.Two families were confirmed by pathological examination and 17 by genetic testing.Of these 17 families, 13 mutations were found.Mutations in exon 11 were found in eight families, in exon 4 were detected in four families, and in exon 13 were found in two families.Mutation in exons 3, 8 and 20 was detected in one family respectively.Most patients presented with stroke and several presented with cognitive decline.Twelve patients had been attacked by risk factors.Magnetic resonance imaging (MRI) was performed on 22 patients.White-matter lesions were distributed in brain stem, basal ganglia, subcortical, temporal pole, external capsule.There were 19 patients with white-matter lesions in temporal pole and seven in capsula externa, showed as a high signal in T2WI.Conclusions CADASIL patients can be associated with risk factors.T2WI hyperintensities in the anterior temporal lobe were more common than that in the capsular external.Exon 11 and exon 4 were the hotspots for the NOTCH3 mutation in Henan patients.

OBJECTIVETo screen the mutation of the beta and gamma subunits of epithelial sodium channel gene SCNN1 in two families with Liddle's syndrome.

METHODSTwo patients clinically diagnosed as Liddle's syndrome and their family members were enrolled. Peripheral blood samples were collected and total genomic DNA was prepared. Polymerase chain reaction (PCR) was used to amplify the exon 13 of the SCNN1B and SCNN1G gene. PCR products were purified and subjected to direct DNA sequencing.

RESULTSA heterozygous nonsense mutation at codon 564 of the SCNN1B gene from CGA(Arg) to stop codon(TGA) was detector in the proband of family 1. More importantly, a novel heterozygous nonsense mutation of CAG(Gln) to stop codon TAG at codon 567 of the SCNN1G gene was detected in the proband and another two members of family 2.

CONCLUSIONScreening for specific mutations of the SCNN1 gene in relatives of patients with Liddle's syndrome can be used to identify the previously unrecognized cases within the family. A new nonsense mutation(Q567X) of the SCNN1G gene is likely the cause of Liddle's syndrome in family 2.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Case-Control Studies ; DNA Mutational Analysis ; Epithelial Sodium Channels ; genetics ; Female ; Humans ; Liddle Syndrome ; genetics ; Male ; Mutation ; genetics ; Pedigree ; Young Adult

OBJECTIVETo study the chemical constituents of the aerial parts of Liusticum chuanxiong.

METHODThe chemical components were isolated by silica gel and Sephadex LH-20 column chromatography. Structures were elucidated on the basis of physico-chemical properities and spectral data.

RESULTEight chemical constituents were isolated, and identified as protocatechuic acid (1), caffeic acid (2), scopoletin (3), apigenin (4), quercetin (5), cosmosiin (6), kaempferol-3-O-beta-D-glucopyranosid (7) and glucose (8).

CONCLUSIONCompounds 1-8 were obtained from the aerial parts of the plant for the first time, compounds 3-8 were obtained from the plant for the first time.

Apigenin ; chemistry ; isolation & purification ; Kaempferols ; chemistry ; isolation & purification ; Ligusticum ; chemistry ; Plant Components, Aerial ; chemistry ; Plants, Medicinal ; chemistry ; Scopoletin ; chemistry ; isolation & purification