Mauritone A, a new polyketide from a fungal-bacterial symbiont Aspergillus spelaeus GXIMD 04541/Sphingomonas echinoides GXIMD 04532.

A new polyketide, mauritone A (1) with six known polyketides curvulone B (2), curvularin (3), 12-oxocurvularin (4), (10E,15S)-10,11-dehydrocurvularin (5), (11R,15S)-11-hydroxycurvularin (6), and (11S,15S)-11-hydroxycurvularin (7) were isolated from the fungal-bacterial symbiont Aspergillus spelaeus GXIMD 04541/Sphingomonas echinoides GXIMD 04532 derived from Mauritia arabica. Their structures were elucidated by extensive spectral analysis. All compounds (1-7) were evaluated for their anti-inflammatory effects. The inhibitory effects of 4, 5, and 7 on nitric oxide (NO) production were found to be significant, with IC50 values of 5.5 ± 0.26, 2.0 ± 0.31, and 8.3 ± 0.62 µM, respectively, surpassing that of the positive control quercetin (10.6 ± 0.64 µM). Compounds 3 and 6 exhibited moderate inhibition of NO, with IC50 values of 18.6 ± 0.53 and 12.7 ± 0.45 µM, respectively.

[Analysis of Curative Efficacy of Different Chemotherapy Regimen Combined with Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation on Multiple Myeloma].

OBJECTIVE: To evaluate the efficacy of autologous peripheral blood hematopoietic stem cell transplantation (auto-PBHSCT) on patients with multiple myeloma( MM) after Sequential different chemotherapy. METHODS: Seven cases of patients with MM were included in the A group, and 14 cases of patients received 4-6 courses of chemotherapy with VAD and MP before transplantation were included in the B group and received 4-6 courses of chemotherapy with VTD and VD before transplantation. Auto-peripheral blood hematopoietic stem cell were mobilized by G-CSF. Condition regimen were melphalan(A group) or bortezomib combined melphalan(B group). IFN-α(A group) or Thalidomide(B group) was used as maintenance treatment after auto-PBHSCT. RESULTS: Two cases of patients reached to complete remission (CR)(2/7,28.6%),1 case got very good partial remission (VGPR) (1/7,14.3%), 4 cases got partial remission(PR) (4/7,57.1%) in A group, and 9 cases got CR (9/14,64.3%), 3 cases got VGPR(3/14,21.4%), and 2 cases got PR(2/14,14.3%) in the B group before auto-PBHSCT. The CR and VGPR were significant difference between 2 groups (P<0.05). All the patients got hematopoietic recovery. In 2 groups, the median time of ANC recovery≥0.5×109/L was 13 (11-16) and 14（11-18）days, that of WBC recovery ≥4.0×109/L were 16(15-19) and 18(16-20)days, Plt recovery ≥ 50 ×109/L was 21 (18-25) and 21(17-25) days. Bone marrow showed CR in 21 to 28 days after transplantation. All of 7 cases of patients remised in 6 to 47 months after transplantation, and 4 cases died lastly and 3 cases failed to be followed up in A group. The median time of progression-free survival(PFS) was 36(6-47) months, and that of overall survival(OS) was 37(7-50) months. In B group, 2 cases of patients remissed in 5 and 17 months after transplantation, and did lastly, 1 case relieved in 12 months after transplantation and failed to be followed up. 1 case of patient relived in 46 months after transplantation, and then received the second auto-PBHSCT, and got CR for 105 months. Other 10 cases got CR, their median time of PFS was 45.5(4-105) months, the median time of overall survival(OS) was 45.5(4-105) months. The PFS and OS were very significant different between 2 groups (P<0.01). CONCLUSION: Bortezomib-based chemotherapy, Auto-PBHSCT and maintenance treatment with thalidomide were favorable to the patients of MM for survival prolongation.

[Clinical Analysis of Adoptive Immunotherapy after Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation in B Lymphocyte Malignant Lymphoma].

OBJECTIVE: To investigate the efficacy of autologous peripheral blood hematopoietic stem cell transplantation(auto-PBHSCT) combined with adoptive immunotherapy for patients with B lymphocyte malignant lymphoma(ML). METHODS: A total of 110 cases of ML treated with adoptive immunotherapy after auto-PBHSCT from January 2000 to December 2009 were enrolled in adoptive immunotherapy group (treated group), while 74 cases of ML treated without adoptive immunotherapy after auto-PBHSCT from January 1995 to December 1999 were used as control group. The efficacy of 2 groups were analyzed and compared, 110 case of ML in treated group included 78 cases of non-Hodgkin's lymphoma(NHL), 32 cases of Hodgkin's lymphoma(HL),74 cases of ML in control group included 52 NHL and 22 HL. All of the patients were treated sequentially with chemotherapy regimens for 6 courses. After that, all the patients received auto-PBHSCT. After hematopoietic reconstruction, the patients in treated group were given 6 courses of adoptive immunotherapy(rhIL-2 100 WU/day for 10 days monthly for each course), while the patients in control group were not given immunotherapy. All the patients were followed-up for more than 5 years. RESULTS: There was one patient in each group, who died of liver failure and cerebral hemorrhage respectively within 3 and 2 months, and all the other patients achieved hematopoietic reconstruction. Following-up for 1, 3, 5 years, the disease-free survival (DFS) rate in treated group was 97.3%,93.6%,87.3% while 91.9%, 73.0%, 64.9% in control group. Following-up for 3 and 5 years, there was very significant difference in DFS between 2 groups(P<0.01). The 1,3 and 5 year DFS rate of patients in stage I/II and III/IV in the treated group were 100%,100%,91.7% and 96.5%,91.9%,86.0% respectively while DFS of control group was 100%, 93.3%, 86.7% and 89.8%, 67.8%, 59.3%, there was a significant difference in 3 and 5 years DFS of III/IV stage patients between 2 groups (P<0.01). The 1,3 and 5 year DFS rate of HL patients were 100%, 93.8%,84.4% in treated group and 100%,72.7%,59.1% in control group respectively. There was significant difference in 3 and 5 years DFS of HL between 2 groups (P<0.05). The 1,3 and 5 year DFS rate of stage I/II HL patients were 100%,100%,88.9% in treated group and 100%,100%,80.0% in control group. The 1,3 and 5 year DFS of HL patients in stage III/IV was 100%,91.3%,82.6% and 94.1%,64.7%,52.9% respectively. There was significant difference in 3 and 5 years DFS of III/IV stage of HL patients between 2 groups (P<0.05). The 1,3 and 5 year DFS rate of NHL patients is 96.2%, 93.6%,88.5% in treated group and 90.4%,73.1%,65.4% in control group respectively. There was a significant difference in 3 and 5 years DFS of NHL between 2 groups(P<0.01). The 1,3 and 5 year DFS rate of stage I/II NHL patients was 100%, 100%, 93.3.9% in treated group and 100%, 90%, 90.0% in control group, respectively. The 1,3 and 5 year DFS of NHL patients in stage III/IV is 95.2%, 92.1%,87.3% and 88.1%,69.0%, 59.5% respectively. There was significant difference in 3 and 5 years DFS of III/IV stage NHL patients between 2 groups (P<0.05). CONCLUSION: Therapeutic efficacy is satisfactory for the patients of B lymphocyte ML treated with adoptive immunotherapy after auto-PBHSCT, especially benefited the patients of stage III/IV significantly.

[Curative efficacy for nasal type extranodal NK/T-cell lymphoma by autologous peripheral blood stem cell transplantation after sequencing chemotherapy and radiotherapy].

The purpose of this study was to explore the curative efficacy for nasal type extranodal NK/T-cell lymphoma by autologous peripheral blood stem cell transplantation (APBSCT) after sequencing chemotherapy and radiotherapy. A total 65 cases diagnosed as nasal type extranodal NK/T-cell lymphoma by pathology and immuno-histochemistry were treated with chemotherapy and radiotherapy in our hospital from January of 2000 to December of 2009. They were divided into observation group (34 cases) and transplantation group (31 cases). The 34 cases of observation group were ceased from treatment, the 31 cases in transplantation group received APBSCT after conditioning regimen with TBI combined VEMAC. Autologous peripheral blood stem cells were mobilized with chemotherapy combined rhG-CSF. The patients were followed up for 3-5 years. The results showed that some side-effects such as bone marrow suppression and injure of oral cavity mucosa were found in patients after sequencing chemotherapy and radiotherapy. All patients in transplantation group obtained hematopoietic reconstruction, and there were no any special side effect such as VOD. In transplantation group, the median time of ANC ≥ 0.5×10(9)/L was 14 (11-17) days, median time of WBC count ≥ 4.0×10(9)/L was 17 (16-20) days, median time of Plt count ≥ 50×10(8)/L were 25 (23-28) days. After chemotherapy and radiotherapy, effective rate of treatment was 91.2% in observation group, whereas was 90.3% in transplantation group, there were no obvious difference between two groups (P > 0.05). After following up about 1 year, effective rate of treatment was 76.5% in observation group, whereas was 96.8% in transplantation group, there were obvious difference between two groups (P < 0.05). After following up about 3 years and 5 years the disease-free survival (DFS) was 61.3%, 43.5% and 87.1%, 81.5% in observation group and transplantation group, there was significant difference between two groups (P < 0.05). It is concluded that treatment with APBSCT after sequencing chemotherapy and radiotherapy for nasal type extranodal NK/T-cell lymphoma may increase DFS efficiently.

[Degradation of orange IV dye solution catalyzed by Fe (NO3)3-(NH4)2S2O8 modified GAC in the presence of H2O2].

This study was designed to investigate the catalytic oxidation performance of modified GAC by Fe(NO3), and (NH4)2S2O8 in the process of H2O2. The effect of the initial concentration of H2O2, initial dye concentration, catalyst dosage, initial pH and temperature on the reaction was discussed. The results show that the catalyst of Fe/S/GAC has a better catalytic reactivity to decompose Orange IV compared with that of Fe/GAC. The catalyst could decompose H2O2 to degrade Orange IV effectively at pH 2.4-9.1. The removal rate of Orange IV increased with the increase of catalyst dosage. With the decrease of dye concentration, the reaction rate became faster, this reaction followed the second-order reaction kinetics with activation energy (Ea) of 68.19 kJ x mol(-1). Reuse of catalyst did not decrease the removal rate. Orange IV degradation mainly followed OH mechanism.

[Efficacy of adoptive immunotherapy after mixed hematopoietic stem cell transplantation on acute myeloid leukemia].

The purpose of this study was to investigate the efficacy of treatment with haploidentical donor's lymphocyte infusion(hiDLI) combined with interleukin-2 (IL-2) after transplantation of autologous peripheral blood stem cells mixed with haploidentical allogeneic bone marrow (mix-HSCT) for acute myeloid leukemia (AML). 49 patients diagnosed as AML were enrolled in this study. After preconditioning with TBI plus VEMAC regimen, all patients received mix-HSCT. Autologous peripheral blood hematopoietic stem cells were mobilized with chemotherapy-combined G-CSF, and haploidentical allogeneic bone marrow cells were not mobilized with G-CSF. 33 patients in test group were treated with hiDLI plus IL-2 for 1-8 times after hematopoietic reconstruction, 16 patients in control group received mix-HSCT only. All the patients were followed-up for more than 3 years. The results showed that all the patients obtained hematopoietic reconstruction, and no graft-versus-host disease (GVHD) was found. In two groups, the median time of absolute neutrophil count (ANC) ≥ 0.5×10(9)/L was 14 (12 - 18) and 14 (11 - 16) days, and WBC count ≥ 4.0×10(9)/L was 17 (16 - 22) and 18(17 - 20) days, Plt count ≥ 50×10(8)/L were 25 (24 - 29) and 25 (23 - 26) days. 9 patients in test group formed mixed chimerism (46XX/46XY) and sustained about 3 - 12 months; disease-free survival (DFS) was 63.6%, 3 patients in control group formed mixed chimerism (46XX/46XY), persistent about 3-6 months; DFS was 50.0%. It is concluded that treatment with hiDLI plus IL-2 after mix-HSCT for AML patients may increase DFS efficiently.

Characterization of a highly polymeric proanthocyanidin fraction from persimmon pulp with strong Chinese cobra PLA2 inhibition effects.

Persimmon proanthocyanidin was fractionated on Toyopearl TSK-HW-50-F to yield a fraction with strong inhibition on the catalytic activity and edema-inducing activity and lethality of Chinese cobra PLA(2). Thiolysis suggested that the terminal units included C, EGCG and myricetin, and epicatechin, epigallocatechin, (epi)gallocatechin-3-O-gallate, and (epi)catechin-3-O-gallate occurred as extender units. The mean degree of polymerization was 23.7. MALDI TOF/MS, thioly-HPLC, FTIR and circular dichroism (CD) analyses showed that the fraction had high prodelphinidin content (55%) and a very high degree of 3-O-galloylation (92%). A type linkage is dominant in it and it had 4ß linkage of the flavanyl substituent and 4R absolute configuration.

High molecular weight persimmon tannin ameliorates cognition deficits and attenuates oxidative damage in senescent mice induced by D-galactose.

Mice were subcutaneously injected with d-galactose (D-gal, 150 mg/kg per day) for 6 weeks and were administered high molecular weight persimmon condensed tannin (HMWPT) simultaneously. After 6 weeks of treatment, the animal behavior was observed in the open field test and water maze test, and the morphology of hippocampus and skin were checked. Meanwhile, the activities of antioxidant enzymes, the levels of non-enzymatic antioxidants, as well as malondialdehyde (MDA) were evaluated. The results indicated that HMWPT markedly inhibited the d-gal induced learning and memory impairment in both open field test and Morris water maze. Biochemical examination revealed that HMWPT significantly increased the decreased activities of superoxide dismutase (SOD), catalase (CAT), elevated the lowered total anti-oxidation capability (T-AOC), glutathione (GSH) and hydroxyproline (Hyp) contents (p<0.01 or p<0.05), and decreased the raised monoamine oxidase (MAO), total cholinesterase (TChE) activities and MDA level (p<0.01) in serum, liver or brain of aging mice induced by d-gal in a dose-dependent fashion. Furthermore, HMWPT significantly and (p<0.01) attenuated the d-gal induced number decrease, neuronal degeneration and karyopycnosis in cells in the hippocampus and decrease of thickness of skin epidermis and dermis.

Correlation between CK18 gene and gastric carcinoma micrometastasis.

AIM: To explore the biological behavior of gastric carcinoma micrometastasis (MM) with a marker of cytokeratin 18 (CK18) and to evaluate the clinical stage of gastric carcinoma and its prognosis. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the expression of CK18 mRNA in 298 lymph nodes from 35 patients with gastric carcinoma and 20 lymph nodes from 10 patients with chronic peptic ulcer and gastric perforation diagnosed by pathological examination and surgery. CK18 mRNA expression of peripheral blood from 54 patients with gastric carcinoma and 10 healthy people were also examined. RESULTS: Expression of CK18 mRNA was not found in 10 patients with benign pathological changes. CK18 mRNA expression in gastric carcinoma tissues was strongly positive. In gastric carcinoma patients, pathological examination revealed that 99 of 298 (33.2%) lymph nodes were positive, while RT-PCR showed that 133 of 298 (44.6%) lymph nodes had expression of CK18 mRNA. The difference was significant (P<0.05). Among the 199 negative lymph nodes identified by pathological examinations, 34 (17.1%) displayed positive expression of CK18 mRNA by RT-PCR. The positive expression of CK18 mRNA was associated with lymph node micrometastasis (LMM) of gastric carcinoma. CK18 mRNA was negatively expressed in all 10 healthy cases and positively expressed in 38.9% of 54 blood specimens from gastric carcinoma patients. The positive rate was not correlated with tumor invasion of gastric carcinoma, but was significantly associated with TNM stage, lymph node metastasis (P=0.0290, P<0.05) and tumor differentiation (P=0.2956, P<0.05). CONCLUSION: RT-PCR with CK18 mRNA as a molecular marker is highly sensitive and specific in detecting LMM of gastric carcinoma. It can benefit the diagnosis of MM and guide studies on biological behavior, clinical phase, and therapy as well as relapse monitoring.

Allogeneic peripheral blood hematopoietic stem cell transplantation in malignant hematopoietic diseases.

To evaluate the use of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) for treatment of acute and chronic leukemia, from March 1997 to January 2003, 21 adult patients with malignant hematopoietic diseases underwent allo-PBSCT from HLA-identical siblings (19 patients) and haplo-identical mother (one) and one B point site mismatched sibling (one). All donors were mobilized with G-CSF for 4 days and peripheral blood stem cells were collected by CS-3000 separator. The conditioning regimen included the high dose combination chemotherapy and TBI. Cyclosporine-A (CsA) plus a short course of MTX was used for GVHD prophylaxis in all patients. The results showed that after trans plantation, median time for the recovery of granuocyte > or = 0.5 x 10(9)/L and platelets > or = 20 x 10(9)/L were 12 (10 - 20) and 15 (11 - 35) days, respectively. Acute GVHD was observed in 8/17 patients (47%), of which one transplanted from HLA-haploidentical mother. Chronic GVHD occurred in 12/17 patients (70%). All of four female survivals did not show acute and chronic GVHD. Day 100 transplantation-related mortality was 14% (3/21). Relapse occurred in two patients (9.5%) who underwent allo-PBSCT in stage of non-remission at one and six months. After follow-up of 40 (15 - 70) months, 11 patients (52.4%) are still disease-free survival. These results suggested that peripheral blood stem cells produce a faster hematopoietic recovery and a lower relapse of leukemia. The rate of aGVHD is not increased when using the peripheral blood as source of stem cells; however, cGVHD continues to be a significant problem. Donors tolerated the procurement procedure without complications.