[Expression and Prognostic Value of Cytokines in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To investigate the expression and prognostic value of cytokines in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). METHODS: Clinical data of 62 patients diagnosed with DLBCL in the First People's Hospital of Yunnan Province from June 2017 to November 2018 were collected. The differences in expression levels of 14 serum cytokines [interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-17F, IL-22, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, TNF-ß] in patients with different survival outcomes, and the impact of the cytokines on 3-year progression-free survival (PFS) and 3-year overall survival (OS) of patients with DLBCL were analyzed retrospectively. RESULTS: Among the 14 cytokines, only the expression of IL-10 was significantly different in patients with different survival outcomes (P =0.007). According to the receiver operating characteristic (ROC) curve, the optimal cut-off value for IL-10 was 11.74 pg/ml. Serum IL-10 was positively correlated with infection markers procalcitonin (PCT) (r =0.321, P =0.029), C-reactive protein (CRP) (r =0.320, P =0.013) and tumor burden index lactate dehydrogenase (LDH) (r =0.439, P <0.001) in newly diagnosed DLBCL patients. The level of IL-10 in patients with pulmonary infection was significantly higher than that in patients without pulmonary infection (P =0.012). However, there was no statistically significant difference on the 3-year survival outcomes between patients with or without pulmonary infection. There was no significant difference in IL-10 level in patients with different Ann Arbor stages (P >0.05). Patients with high IL-10 level (IL-10>11.74 pg/ml) had significantly higher LDH level than those with low IL-10 level (IL-10≤11.74 pg/ml) (P <0.001). The 3-year PFS rate and 3-year OS rate of DLBCL patients with high IL-10 level were significantly lower than those of low IL-10 level group [(44.4±11.7)% vs (81.8±5.8)%, P <0.001; (61.6±11.5)% vs (93.2±3.8)%, P =0.001]. CONCLUSION: Serum IL-10 level in newly diagnosed DLBCL patients can reflect the inflammatory state of the body, which may be related to tumor load. Newly diagnosed DLBCL patients with serum IL-10>11.74 pg/ml have higher early mortality and worse prognosis.

Use of adeno-associated virus-mediated delivery of mutant huntingtin to study the spreading capacity of the protein in mice and non-human primates.

In order to model various aspects of Huntington's disease (HD) pathology, in particular protein spread, we administered adeno-associated virus (AAV) expressing green fluorescent protein (GFP) or GFP coupled to HTT-Exon1 (19Q or 103Q) to the central nervous system of adult wild-type (WT) mice and non-human primates. All animals underwent behavioral testing and post-mortem analyses to determine the long-term consequences of AAV injection. Both mice and non-human primates demonstrated behavioral changes at 2-3 weeks post-surgery. In mice, these changes were absent after 3 months while in non-human primates, they persisted in the majority of tested animals. Post-mortem analysis revealed that spreading of the aggregates was limited, although the virus did spread between synaptically-connected brain regions. Despite circumscribed spreading, the presence of mHTT generated changes in endogenous huntingtin (HTT) levels in both models. Together, these results suggest that viral expression of mHTTExon1 can induce spreading and seeding of HTT in both mice and non-human primates.

Supramolecular Isomers of Coordination-Directed Side-Chain Polypseudorotaxanes Based on Trimeric Uranyl Oxalate Nodes.

Although the prosperity of rotaxane coordination polymers with rotaxane molecules serving as main-chain linkers is known, side-chain metal-organic polypseudorotaxanes incorporating macrocyclic host molecules have not been reported to date. Herein a new type of coordination-driven cucurbit[6]uril-bearing side-chain polypseudorotaxane, with two-dimensional trimeric uranyl-oxalate as main chains, has been synthesized. This was carried out through hydrothermal reactions of uranyl components with an in situ-formed carboxylated pseudorotaxane ligand in the presence of oxalate co-ligands. Varying the substitution site of coordination groups led to two different supramolecular isomers. Further mechanistic analysis indicated that condition-dependent hydrolysis of the cyano groups of the pseudorotaxane ligand, as well as the participation of oxalate groups into the coordination sphere of uranyl moieties, contributes to the formation of this new type of side-chain polypseudorotaxane.

The recombinant N-terminal domain of spike proteins is a potential vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV) infection.

The persistent public health threat of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the need for an effective MERS-CoV vaccine. Previous studies have focused mainly on the receptor-binding domain (RBD) on the spike protein of MERS-CoV. Herein, we investigated the immunogenicity and protective potential of the recombinant N-terminal domain (rNTD) of spike proteins as a vaccine candidate. BALB/c mice vaccinated with 5 or 10µg of rNTD protein demonstrated a significant humoral immune response (serum IgG and neutralizing activity). Additionally, according to the enzyme-linked immunospot, intracellular cytokine staining, and cytometric bead array assays, significant and functional T-cell immunity was induced by 10µg of the rNTD vaccination with aluminum and CpG adjuvant. Furthermore, rNTD-immunized mice showed reduced lung abnormalities in a MERS-CoV-challenge mouse model transfected with an adenoviral vector expressing human DPP4, showing protection consistent with that found with rRBD vaccination. These data show that rNTD induced potent cellular immunity and antigen-specific neutralizing antibodies in mice and that it demonstrated protective capacity against a viral challenge, indicating that rNTD is a vaccine candidate against MERS-CoV infection.

Valproic acid (VPA) enhances cisplatin sensitivity of non-small cell lung cancer cells via HDAC2 mediated down regulation of ABCA1.

Valproic acid (VPA) has been suggested to be a histone deacetylase inhibitor (HDACI). Our present study revealed that VPA at 1 mm, which had no effect on cell proliferation, can significantly increase the sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin (DDP). VPA treatment markedly decreased the mRNA and protein levels of ABCA1, while had no significant effect on ABCA3, ABCA7 or ABCB10. Luciferase reporter assays showed that VPA can decrease the ABCA1 promoter activity in both A549 and H358 cells. VPA treatment also decreased the phosphorylation of SP1, which can bind to -100 and -166 bp in the promoter of ABCA1. While the phosphorylation of c-Fos and c-Jun were not changed in VPA treated NSCLC cells. Over expression of HDAC2 attenuated VPA induced down regulation of ABCA1 mRNA expression and promoter activities. Over expression of HDAC2 also attenuated VPA induced DDP sensitivity of NSCLC cells. These data revealed that VPA can increase the DDP sensitivity of NSCLC cells via down regulation of ABCA1 through HDAC2/SP1 signals. It suggested that combination of VPA and anticancer drugs such as DDP might be great helpful for treatment of NSCLC patients.

Risk factors for postoperative delirium in patients after coronary artery bypass grafting: A prospective cohort study.

PURPOSE: This study was designed to identify the incidence and independent perioperative risk factors associated with postoperative delirium of patients who underwent coronary artery bypass grafting (CABG) in a large intensive care unit setting in China. METHODS: Delirium was diagnosed by the confusion assessment method for the intensive care unit (CAM-ICU). Baseline demographics, perioperative data, and postoperative outcomes of 249 consecutive patients who underwent CABG were recorded prospectively and analyzed via univariate analysis and multivariate logistic regression to determine the independent risk factors of postoperative delirium. RESULTS: Postoperative delirium was detected in 76 patients according to CAM-ICU criteria. The incidence was 30.52%. Patients with and without delirium differed significantly on 34 variables (P < .05). Multivariate logistic regression analysis revealed that preoperative atrial fibrillation (odds ratio [OR], 3.957; 95% confidence interval [CI], 1.727-9.066), elevated European system for cardiac operative risk evaluation (OR, 1.178; 95% CI, 1.018-1.364), cognitive impairment (OR, 3.231; 95% CI, 1.008-10.356), prolonged surgery duration (OR, 1.008; 95% CI, 1.003-1.014), postoperative poor quality of sleep (OR, 5.001; 95% CI, 2.476-10.101), and electrolyte disturbance (OR, 2.095; 95% CI, 1.041-4.216) were independently associated with postoperative delirium after CABG. CONCLUSIONS: Delirium is a frequent complication. Factors independently associated with delirium are preoperative atrial fibrillation, elevated European system for cardiac operative risk evaluation and cognitive impairment, longer surgery duration, postoperative poor quality of sleep, and electrolyte disturbance. The study may be helpful in decreasing the incidence of postoperative delirium after CABG by treating these predictors properly.

Azithromycin attenuates pulmonary inflammation and emphysema in smoking-induced COPD model in rats.

INTRODUCTION: The role of inflammation and immunity in COPD treatment is increasingly being recognized. The relationship between anti-inflammation/immunoregulation and emphysema in COPD lungs remains to be elucidated. The aim of this study was to investigate the effects of azithromycin (Azm) on the development of emphysema in smoking-induced COPD in rats. METHODS: Sprague-Dawley rats (n = 50) were randomly assigned to normal, COPD, saline-treated, Azm-treated, and levofloxacin-treated (Lev) groups. The effects of treatment were assessed by measuring the levels of vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assay and measuring the numbers of neutrophil and macrophage in bronchoalveolar lavage fluid, vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR2) protein expression by western blotting. Lung function measurements and histopathological evaluations (mean linear intercept and destructive index) were performed. RESULTS: FEV0.3/FVC and peak expiratory flow were lower in the COPD group than in the normal group. Mean linear intercept and destructive index were lower in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. The numbers of neutrophil and macrophage in bronchoalveolar lavage fluid were lower in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. As confirmed by western blotting, the levels of VEGF in lung homogenates were higher in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. VEGFR2 protein expression was higher in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. CONCLUSIONS: Azm attenuates pulmonary emphysema by partly reversing the decrease in the numbers of inflammatory cells (neutrophil and macrophage) and VEGF secretion and VEGFR2 protein expression in smoking-induced COPD in rats.

Interventional therapy for human breast cancer in nude mice with 131I gelatin microspheres (¹³¹I-GMSs) following intratumoral injection.

INTRODUCTION: The aim of this study was to investigate the effects of 131I gelatin microspheres (131I-GMS) on human breast cancer cells (MCF-7) in nude mice and the biodistribution of 131I-GMSs following intratumoral injections. METHODS: A total of 20 tumor-bearing mice were divided into a treatment group and control group and received intratumoral injections of 2.5 mci 131I-GMSs and nonradioactive GMSs, respectively. Tumor size was measured once per week. Another 16 mice received intratumoral injections of 0.4 mci 131I-GMSs and were subjected to single photon emission computed tomography (SPECT) scans and tissue radioactivity concentration measurements on day 1, 4, 8 and 16 postinjection. The 20 tumor-bearing mice received intratumoral injections of 0.4 mci [131I] sodium iodide solution and were subjected to SPECT scans and intratumoral radioactivity measurements at 1, 6, 24, 48 and 72 h postinjection. The tumors were collected for histological examination. RESULTS: The average tumor volume in the 131I-GMSs group on post-treatment day 21 decreased to 86.82 ± 63.6%, while it increased to 893.37 ± 158.12% in the control group (P < 0.01 vs. the 131I-GMSs group). 131I-GMSs provided much higher intratumoral retention of radioactivity, resulting in 19.93 ± 5.24% of the injected radioactivity after 16 days, whereas the control group retained only 1.83 ± 0.46% of the injected radioactivity within the tumors at 1 h postinjection. CONCLUSIONS: 131I-GMSs suppressed the growth of MCF-7 in nude mice and provided sustained intratumoral radioactivity retention. The results suggest the potential of 131I-GMSs for clinical applications in radiotherapy for breast cancer.

Effect of (131)I gelatin microspheres on hepatocellular carcinoma in nude mice and its distribution after intratumoral injection.

In this study, we investigated the effect of (131)I gelatin microspheres ((131)I-GMSs) on human hepatocellular carcinoma cells (HepG2) in nude mice (Balb/c) and the biodistribution of (131)I-GMSs after intratumoral injection. The treatment group and control group animals received intratumoral injections of 1 mCi (131)I-GMSs and GMSs unlabeled (131)I, respectively. The size of the implanted tumor was measured once a week for 8 weeks, and the survival time was calculated from the day of injection to 64 days post-injection. Another 35 animals received intratumoral injections of 0.2 mCi (131)I-GMSs and were subject to single-photon emission computed tomography (SPECT) on days 1, 8, 16, 24 and 32 post-injection. Samples of various organs were collected and used to calculate tissue concentrations on days 1, 4, 8, 16 and 24. Free thyroxine (FT4) in fetal bovine serum was tested to evaluate thyroid function. The tumors were collected for histological examination. (131)I-GMSs produced a pronounced reduction in HepG2 tumor volume, and the overall survival was 73.3% in the treatment group and only 13.3% in the control group (P < 0.001). Tissue radioactivity concentration measurements and SPECT demonstrated that the injected (131)I-GMSs mainly accumulated within the tumors. The concentration of FT4 was stable during the observation period. The microspheres could be observed by histological methods on day 32. (131)I-GMSs suppressed the growth of HepG2 in the nude mice and were retained in the tumor for a long period of time after injection. Direct intratumoral injection of (131)I-GMSs offers a promising modality for the treatment of hepatocellular carcinoma.

Association between estrogen receptor alpha c.454-397T>C and c.454-351A>G and ischemic stroke risk: a systematic review and meta-analysis.

The association between estrogen receptor alpha (ESR1) c.454-397T>C and c.454-351A>G polymorphism and ischemic stroke remains controversial. The aim of this study was to perform a meta-analysis to investigate a more authentic association between c.454-397T>C and c.454-351A>G mutation and ischemic stroke. Systematic searches of electronic databases Embase, PubMed, Web of Science as well as hand-searching of the references of identified articles and the meeting abstracts were performed. Study selection, data abstraction and study quality evaluation were independently conducted in duplicate. Statistical analyses were performed using software Stata 11.0. The pooled odds ratios (ORs) with 95 % confidence intervals (95 % CIs) were performed. Different effect models were used according to the difference in heterogeneity. Publication bias was tested by Begg's funnel plot and Egger's regression test. For c.454-397T>C mutation, five studies were combined. Significant association was found in allelic model (OR = 1.12, 95 % CI = 1.01-1.25, p = 0.03), additive model (OR = 1.25, 95 % CI = 1.01-1.54, p = 0.04), and recessive model (OR = 1.23, 95 % CI = 1.02-1.49, p = 0.03), whereas no evidence of association was found for dominant model (OR = 1.10, 95 % CI = 0.85-1.42, p = 0.47). For c.454-351A>G mutation, no evidence of association was found for all genetic models. Our meta-analysis suggests that ESR1 c.454-397T>C mutation is significantly associated with increased risk of ischemic stroke, whereas no evidence of association was found for ESR1 c.454-351A>G mutation.

Simultaneous determination and pharmacokinetic analysis of seven alkaloids and two flavonoids from rat plasma by HPLC-DAD after oral administration of Wuzhuyu decoction.

A simple and sensitive high-performance liquid chromatographic method was developed for the simultaneous determination and pharmacokinetic analysis of seven alkaloids dehydroevodiamine (DHED), 10-hydroxyrutaecarpine (HDR), evodiamine (EDM), rutaecarpine (RCP), 1-methyl-2-n-nonyl-4(1H)quinolone (MNQ), evocarpine (ECP), and dihydroevocarpine (DHE), and two flavonoids isorhamnetin-7-O-rutinoside (RIM) and diosmetin-7-O-ß-d-glucopyranoside (GRD) in rat plasma after oral administration of Wuzhuyu decoction. The flow rate was kept at 1.0 ml/min and the detection wavelength was set at 300 nm. The calibration curves were linear in the range of 0.5013-30.076 µg/ml for DHED, 0.2161-21.608 µg/ml for RIM, 0.161-12.876 µg/ml for HDR, 0.2146-21.457 µg/ml for GRD, 2.0464-40.928 µg/ml for EDM, 1.0398-31.194 µg/ml for RCP, 0.5970-35.818 µg/ml for MNQ, 0.8371-20.928 µg/ml for ECP, and 0.5167-31.003 µg/ml for DHE. The precision (relative standard deviation (RSD), %) for all was less than 10% and the accuracy (relative error (RE), %) was within ± 10%. The results demonstrated that the assay had remarkable reproducibility with acceptable accuracy and precision. The lower limit of quantifications for the compounds in plasma ranged from 0.12 to 0.23 µg/ml and the lower limit of detections ranged from 0.024 to 0.076 µg/ml. This validated method has been successfully applied in the pharmacokinetics study of seven alkaloids and two flavonoids after orally administrating the Wuzhuyu decoction to rats.

[Clinical characteristics and risk factors of hemodynamic depression after carotid angioplasty and stenting].

OBJECTIVE: To investigate the carotid angioplasty and stenting (CAS)-induced hemodynamic depression (HD) and its impact on postprocedural complications so as to identify its risk factors. METHODS: The incidence, onset time, duration and severity of HD were observed in 196 CAS patients. The influences of clinical baseline and vascular angiographic characteristics on HD were recorded and the relationship between HD and postprocedural complications was analyzed. Logistic regression analysis was used to identify the independent risk factors of HD. RESULTS: The incidence of HD was 53.1%. Most cases of HD (67.3%) developed within 1 - 16 hours postprocedural. And 55.8% HD lasted for over 24 hours and became relieved within 3 - 16 days post-operation. And 78.9% HD patients required medications for the controls of blood pressure and heart rate. Diabetes, hypertension, smoking, plaque involving carotid bulb, ulcerated plaque and calcified plaque were shown to be associated with HD. Further analysis of logistic regression suggested that diabetes and smoking were two protective factors for HD while plaque involving carotid bulb and calcified plaque two independent risk factors for HD. The HD patients were at an increased risk of neurological and cardiopulmonary complications. CONCLUSION: With a high post-CAS incidence after CAS, HD is associated with postprocedural complications. Lesions involving carotid bulb and calcified plaque are two independent risk factors for HD.

Cerebral ischemia aggravates cognitive impairment in a rat model of Alzheimer's disease.

AIM: Autopsy evidence suggests that the presence of both Alzheimer(')s disease (AD) and cerebral infarction pathology is associated with more severe cognitive impairment than that produced by AD pathology alone. This study aims to investigate the effect of cerebral ischemia on cognitive function in rats with AD constructed by hippocampal injection and to determine its underlying mechanism, which is proposed to be of significance to the treatment of AD. MAIN METHODS: AD was modeled by injection of aggregated Aß(1-40), either alone or followed by hippocampal endothelin-1 injection to mimic cerebral ischemia in hippocampus, into the right dentate gyrus (DG) of rats. The Morris water maze was used to evaluate cognitive function. Aß deposition, neuronal loss and phosphorylated tau expression in hippocampus were examined by Congo red staining, Nissl's staining and immunohistochemistry, respectively. Reactive astrocytes, IL-1ß and TNF-α expressions were measured by immunohistochemistry, in situ hybridization and reverse transcription-polymerase chain reaction. KEY FINDINGS: Compared with rats treated with either Aß or endothelin alone, rats treated with both Aß and endothelin showed more aggravated cognitive impairment and more Aß deposits, neuron loss, phosphorylated tau expression, reactive astrocytes, IL-1ß and TNF-α expressions in hippocampus. SIGNIFICANCE: Hippocampal ischemia aggravates cognitive impairment of AD rats by increasing Aß deposits, neuron loss and tau phosphorylation in hippocampus. The enhanced inflammatory response may be responsible for cerebral ischemia-induced aggravation of cognitive impairment in AD rats. Based on these findings, prevention and treatment of cerebral ischemia may improve clinical symptoms of AD and suppress the progression of AD.

Fully human monoclonal antibody directed to proteolytic cleavage site in severe acute respiratory syndrome (SARS) coronavirus S protein neutralizes the virus in a rhesus macaque SARS model.

BACKGROUND: There is still no effective method to prevent or treat severe acute respiratory syndrome (SARS), which is caused by SARS coronavirus (CoV). In the present study, we evaluated the efficacy of a fully human monoclonal antibody capable of neutralizing SARS-CoV in vitro in a Rhesus macaque model of SARS. METHODS: The antibody 5H10 was obtained by vaccination of KM mice bearing human immunoglobulin genes with Escherichia coli-producing recombinant peptide containing the dominant epitope of the viral spike protein found in convalescent serum samples from patients with SARS. RESULTS: 5H10, which recognized the same epitope that is also a cleavage site critical for the entry of SARS-CoV into host cells, inhibited propagation of the virus and pathological changes found in Rhesus macaques infected with the virus through the nasal route. In addition, we analyzed the mode of action of 5H10, and the results suggested that 5H10 inhibited fusion between the virus envelope and host cell membrane. 5H10 has potential for use in prevention and treatment of SARS if it reemerges. CONCLUSIONS: This study represents a platform to produce fully human antibodies against emerging infectious diseases in a timely and safe manner.

[Preparation and biological characteristics of a new doxorubicin-gelatin-microspheres for hepatic artery embolization].

OBJECTIVE: To prepare a new doxorubicin-gelatin-microspheres (DR-GMs) suitable for hepatic artery chemoembolization. METHODS: Oxidized dextran and glutaraldehyde were used respectively as crosslinking agent for preparing DR-GMs. Orthogonal design was employed to optimize the preparation of the oxidized dextran cross-linked GMs. The morphology, swelling, and in vitro and in vivo degrading were compared between the two groups of microspheres, both with 60% degree of cross-linking. RESULTS: The granulometers of both groups of microspheres fitted for hepatic artery embolization. The roundness of the microspheres (observed with scanning electron microscope) crosslinked by oxidized-dextran was better than those crosslinked by glutaraldehyde. The microspheres crosslinked by oxidized-dextran had an average diameter of (78.2 +/- 8.1) microm, and a narrow size distribution (76.4 +/- 3.2)%, which ranged from 50 to 125 microm. The drug content rate and encapsulation rate of the microspheres crosslinked by oxidized-dextran were (87.5 +/- 0.9)% and (12.2 +/- 1.1)% respectively, higher than those crosslinked by glutaraldehyde (P < 0.01). The cumulative release rate of doxorubicin from the microspheres crosslinked by oxidized-dextran in 12 hours was 83.2%, lower than that from the microspheres crosslinked by glutaraldehyde (P < 0.01). The in vitro and in vivo studies found that the duration of degradation of the microspheres crosslinked by oxidized-dextran appeared longer than those crosslinked by glutaraldehyde. CONCLUSION: Oxidized-dextran is a better crosslinking agent for preparing DR-GMs, because it has more advantages over glutaraldehyde as for hepatic artery chemoembolization.

Direct in vivo injection of 131I-GMS and its distribution and excretion in rabbit.

AIM: To explore the distribution and metabolism of (131)I-gelatin microspheres ((131)I-GMSs) in rabbits after direct injection into rabbits' livers. METHODS: Twenty-eight healthy New Zealand rabbits were divided into seven groups, with four rabbits per group. Each rabbit's hepatic lobes were directly injected with 41.336 +/- 5.106 MBq (131)I-GMSs. Each day after (131)I-GMSs administration, 4 rabbits were randomly selected, and 250 microL of serum was collected for gamma count. Hepatic and thyroid functions were tested on days 1, 4, 8, 16, 24, 32, 48 and 64 after (131)I-GMSs administration. Single-photon emission computed tomography (SPECT) was taken for each group on days 0, 1, 4, 8, 16, 24, 32, 48, 64 after (131)I-GMSs administration. A group of rabbits were sacrificed respectively on days 1, 4, 16, 24, 32, 48, 64 after (131)I-GMSs administration. Their livers were taken out for histological examination. RESULTS: After (131)I-GMSs administration, the nuclide was collected in the hepatic area with microspheres. The radiation could be detected on day 48 after (131)I-GMSs administration, and radiography could be seen in thyroid areas in SPECT on days 4, 8, 16 and 24. One day after (131)I-GMSs administration, the liver function was damaged but recovered 4 d later. Eight days after (131)I-GMSs administration, the levels of free triiodothyronine and free thyroxin were reduced, which restored to normal levels on day 16. Histological examination showed that the microspheres were degraded to different degrees at 24, 32 and 48 d after (131)I-GMSs administration. The surrounding parts of injection points were in fibrous sheathing. No microspheres were detected in histological examination on day 64 after (131)I-GMSs administration. CONCLUSION: Direct in vivo injection of (131)I-GMSs is safe in rabbits. It may be a promising method for treatment of malignant tumors.

Synthesis and DNA-cleavage properties of metal complexes of 1,4,7,10-tetraazacyclododecane (cyclen) functionalized with a pendant benzocrown ether.

The synthesis and DNA-cleavage properties of a series of novel mononuclear Zn(II), Cu(II), and Co(II) complexes 2 of a crown-ether-functionalized cyclen ligand is described. The Cu complex 2b displayed the highest catalytic activity towards pUC 19 DNA. The effects of reaction time, complex concentration, and pH were investigated, showing that 2b readily and efficiently converts supercoiled (type I ) plasmid DNA to nicked (type II) DNA under physiological conditions (37 degrees, pH 7.4).

Homing efficiency and hematopoietic reconstitution of bone marrow-derived stroma cells expanded by recombinant human macrophage-colony stimulating factor in vitro.

The increasing recognition of the properties of marrow stromal cells has spawned a major switch in our perception of their nature and the potential therapeutic applications that have been envisioned and implemented. Yet, several aspects of bone marrow stromal cell biology remain in question. This report describes the ability of recombinant human macrophage colony-stimulating factor (rhM-CSF) to maintain proliferation and differentiation of bone marrow stromal cells ex vivo. Our results demonstrated that M-CSF was essential for proliferation and differentiation of bone marrow-derived stromal cells and exerted its effects in a dose-dependent manner. The number of colony-forming unit (CFU) fibroblasts increased by 25% after incubation with rhM-CSF. In vitro expanded bone marrow stromal cells were easy to passage and differentiated to adipocyte and chondroblast cells under appropriate culture conditions. Furthermore, these expanded stromal cells to support CD34+ hematopoietic stem cells, as demonstrated by their ability to form CFU-Mix, burst-forming units-erythroid, and CFU-granulocyte macrophage colonies after 3 weeks of culture. The homing efficiency of in vitro expanded or fresh isolated bone marrow-derived stromal cells, which were labeled with carboxy fluorescein diacetate succinimidyl ester, to bone marrow was also investigated. Homing assays demonstrated that freshly isolated CD45+-depleted bone marrow cells were able to home to bone marrow in a dose-dependent manner, although some cells were found in the spleen, liver, and lung. However, their ability to home was dramatically reduced with culture time and was completely lost after five to seven passages in vitro. Animal studies showed that freshly isolated or rhM-CSF-induced bone marrow stromal cells promoted hematopoietic reconstitution in lethally irradiated mice. The ability to easily expand human stromal cells, which support survival and proliferation of CD34+ cells, has many important clinical applications for hematopoietic disorders.