Abstract:Dendritic cells (DCs), the most prevalent antigen-presenting cell in vivo, had been widely characterized in the last three decades. DCs are present in almost all tissues of the body and play cardinal roles in recognition of microbial agents, autoantigens, allergens and alloantigen. DCs process the microbial agents or their antigens and migrate to lymphoid tissues to present the antigenic peptide to lymphocytes. This leads to activation of antigen-specific lymphocytes. Initially, it was assumed that DCs are principally involved in the induction and maintenance of adaptive immune responses, but now it is evident that DCs also have important roles in innate immunity. These features make DCs very good candidates for therapy against various pathological conditions including malignancies. Initially, DC-based therapy was used in animal models of cancers. Data from these studies inspired considerable optimism and DC-based therapies was started in human cancers 8 years ago. In general, DC-based therapy has been found to be safe in patients with cancers, although few controlled trials have been conducted in this regard. Because the fundamentals principles of human cancers and animal models of cancers are different, the therapeutic efficacy of the ongoing regime of DC-based therapy in cancer patients is not satisfactory. In this review, we covered the various aspects that should be considered for developing better regime of DC-based therapy for human cancers.
Keywords:Dendritic cells;Cancer immunology;DC-based therapy;Safety;Efficacy;Animal model of cancers;Human cancers
Abstract:To screen and evaluate protein biomarkers for the detection of gliomas (Astrocytoma grade I–IV) from healthy individuals and gliomas from brain benign tumors by using surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) coupled with an artificial neural network (ANN) algorithm. SELDI-TOF-MS protein fingerprinting of serum from 105 brain tumor patients and healthy individuals, included 28 patients with glioma (Astrocytoma I–IV), 37 patients with brain benign tumor, and 40 age-matched healthy individuals. Two thirds of the total samples of every compared pair as training set were used to set up discriminating patterns, and one third of total samples of every compared pair as test set were used to cross-validate; simultaneously, discriminate-cluster analysis derived SPSS 10.0 software was used to compare Astrocytoma grade I–II with grade III–IV ones. An accuracy of 95.7%, sensitivity of 88.9%, specificity of 100%, positive predictive value of 90% and negative predictive value of 100% were obtained in a blinded test set comparing gliomas patients with healthy individuals; an accuracy of 86.4%, sensitivity of 88.9%, specificity of 84.6%, positive predictive value of 90% and negative predictive value of 85.7% were obtained when patient’s gliomas was compared with benign brain tumor. Total accuracy of 85.7%, accuracy of grade I–II Astrocytoma was 86.7%, accuracy of III–IV Astrocytoma was 84.6% were obtained when grade I–II Astrocytoma was compared with grade III–IV ones (discriminant analysis).
Abstract:Objective:To construct a eukaryotic expression plasmid pcDNA3.1(-)-Humanin.Methods:The recombinant plasmid pGEMEX-1-Humanin was digested with restriction endonucleases BamH I and Hind III and the Humanin gene fragments, about 100 bp length, were obtained. Then the Humanin gene fragments were inserted into eukaryotic expression vector pcDNA3.1(-) and the recombinant plasmids pcDNA3.1(-)-Humanin were identified by sequencing.Results:Recombinant plasmid DNA successfully produced a band which had the same size as that of the Humanin positive control. The sequence of recombinant plasmids accorded with the Humnain gene sequence.Conclusions:A eukaryotic expression plasmid of Humanin was successfully constructed.
Abstract:Objectives:To investigate the intestinal microflora status related to ischemia/reperfusion (I/R) liver injury and explore the possible mechanism.Methods:Specific pathogen free grade Sprague-Dawley rats were randomized into three groups: Control group (n=8), sham group (n=6) and I/R group (n=10). Rats in the control group did not receive any treatment, rats in the I/R group were subjected to 20 min of liver ischemia, and rats in the sham group were only subjected to sham operation. Twenty-two hours later, the rats were sacrificed and liver enzymes and malondialdehyde (MDA), superoxide dismutase (SOD), serum endotoxin, intestinal bacterial counts, intestinal mucosal histology, bacterial translocation to mesenteric lymph nodes, liver, spleen, and kidney were studied.Results:Ischemia/reperfusion increased liver enzymes, MDA, decreased SOD, and was associated with plasma endotoxin elevation in the I/R group campared to those in the sham group. Intestinal Bifidobacteria and Lactobacilli decreased and intestinal Enterobacterium and Enterococcus, bacterial translocation to kidney increased in the I/R group compared to the sham group. Intestinal microvilli were lost, disrupted and the interspace between cells became wider in the I/R group.Conclusion:I/R liver injury may lead to disturbance of intestinal microflora and impairment of intestinal mucosal barrier function, which contributes to endotoxemia and bacterial translocation to kidney.
Abstract:Objective:To investigate the role of 99mTc-TRODAT-1 SPECT in diagnosis and assessing severity of idiopathic Parkinson’s disease (PD).Methods:Thirty-eight patients with primary, tentative diagnosis of PD and eighteen age-matched normal controls were studied with 99mTc-TRODAT-1 SPECT imaging. The regions of interests (ROIs) were drawn manually on cerebellum (CB), occipital cortex (OC) and three transverse plane slice-views of striatums, the semiquantitative BG (background)/[(OC+CB)/2] were then calculated.Results:A lower uptake of 99mTc-TRODAT-1 in striatums were displayed in thirty-six out of thirty-eight PD patients by visual inspection, compared to controls. In twenty-four PD cases with HYS (Hoehn and Yahr scale) stage I, a greater loss of DAT uptake was found in striatum and its subregions contralateral striatum to the affected limbs than in the same regions of the controls, although the striatal uptake was bilaterally reduced. Using Spearman correlation analysis showed that the reduction of the uptake ratios significantly correlated with the UPDRS in striatum and all its subregions in the PD group (P<0.05), a similar change was also found in the putamen by using the rating scale of Hoehn and Yahr (P<0.05). However, analysis of variance (ANOVA) did not show any relationship between the decreasing uptake of 99mTc-TRODAT-1 and increasing severity of PD patients, although the specific uptake of 99mTc-TRODAT-1 was continuously decreased in the striatum by visual inspection with the progress of PD from HYS stage I to III.Conclusion:99mTc-TRODAT-1 SPECT imaging may serve as a useful method for improving the correct diagnosis of PD. In assessing the role of 99mTc-TRODAT-1 SPECT in disease severity of PD, UPDRS can offer a comprehensive index, although the Hoehn and Yahr assessment may be available in part.
Abstract:To investigate the inhibiting effect of β-Aescin on nuclear factor-κB (NF-κB) activation and the expression of tumor necrosis factor-α (TNF-α) protein after traumatic brain injury (TBI) in the rat brain, 62 SD rats were subjected to lateral cortical impact injury caused by a free-falling object and divided randomly into four groups: (1) sham operated (Group A); (2) injured (Group B); (3) β-Aescin treatment (Group C); (4) pyrrolidine dithocarbamate (PDTC) treatment (Group D). β-Aescin was administered in Group C and PDTC treated in Group D immediately after injury. A series of brain samples were obtained directly 6 h, 24 h and 3 d respectively after trauma in four groups. NF-κB activation was examined by Electrophoretic Mobility Shift Assay (EMSA); the levels of TNF-α protein were measured by radio-immunoassay (RIA); the water content of rat brain was measured and pathomorphological observation was carried out. NF-κB activation, the levels of TNF-α protein and the water content of rat brain were significantly increased (P<0.01) following TBI in rats. Compared with Group B, NF-κB activation (P<0.01), the levels of TNF-α protein (P<0.01) and the water content of brain (P<0.05) began to decrease obviously after injury in Groups C and D. β-Aescin could dramatically inhibit NF-κB activation and the expression of TNF-α protein in the rat brain, alleviate rat brain edema, and that could partially be the molecular mechanism by which β-Aescin attenuates traumatic brain edema.
Abstract:Objective:To characterize the expression of aquaporin-4 (AQP4), one of the aquaporins (AQPs), in human brain specimens from patients with traumatic brain injury or brain tumors.Methods:Nineteen human brain specimens were obtained from the patients with traumatic brain injury, brain tumors, benign meningioma or early stage hemorrhagic stroke. MRI or CT imaging was used to assess brain edema. Hematoxylin and eosin staining were used to evaluate cell damage. Immunohistochemistry was used to detect the AQP4 expression.Results:AQP4 expression was increased from 15 h to at least 8 d after injury. AQP4 immunoreactivity was strong around astrocytomas, ganglioglioma and metastatic adenocarcinoma. However, AQP4 immunoreactivity was only found in the centers of astrocytomas and ganglioglioma, but not in metastatic adenocarcinoma derived from lung.Conclusion:AQP4 expression increases in human brains after traumatic brain injury, within brain-derived tumors, and around brain tumors.
Abstract:Objective:To observe the clinicopathological characteristics of gastric stump cancer (GSC) and evaluate the benefits of radical surgery of GSC.Methods:The clinicopathological characteristics and postoperative survival time of 37 GSC patients who underwent surgery were investigated retrospectively. The survival time was compared according to the type of surgical operation (radical resection vs palliative operation). Twenty-one cases that received radical resection were analyzed based on the pTMN stage. Survival curves were traced by using Kaplan-Meier methods.Results:Most GSC (32/37) was detected in patients who had received Billroth II reconstruction after partial gastrectomy for benign gastric disease. The lesser curvature side and the suture line of anastomosis were the most frequent sites where GSC occurred (27/37). Differentiated adenocarcinoma was the dominant histopathological type (24/37). The postoperative 5-year survival rate of early stage GSC patients (n=9) was significantly higher than advanced stage GSC (n=12) (55.6% vs 16.5%, xL2=11.48, P<0.01). Five-year survival rate of 21 GSC patients with radical resection were 75% (3/4) for stage I, 60% (3/5) for stage II, 14.2% (1/7) for stage III, and 0% (0/5) for stage IV respectively. The median survival time of 21 GSC patients who underwent radical resection was longer than those undergoing palliative operation (43.0 m vs 13.0 m, xL2=36.31, P<0.01), the median survival time of stage IV patients with radical resection was 23.8 months.Conclusions:Without remote metastasis, radical resection for GSC is possible, and is an effective way to improve the prognosis of GSC. Even in stage IV GSC, radical resection can still prolong the survival time. It is necessary for the patients with benign gastric diseases who received partial gastrectomy to carry out the endoscopy follow-up, especially in patients with Billroth II reconstruction procedure at 15–20 years.
Abstract:Objective:To evaluate the predictive performance of ‘Diprifusor’ TCI (target-controlled infusion) system for its better application in clinical anesthesia.Methods:The predictive performance of a ‘Diprifusor’ TCI system was investigated in 27 Chinese patients (16 males and 11 females) during upper abdominal surgery under total intravenous anesthesia (TIVA) with propofol/fentanyl. Measured arterial propofol concentrations were compared with the values predicted by the TCI infusion system. Performance was determined by the median performance error (MDPE), the median absolute performance error (MDAPE), the divergence (the percentage change of the absolute PE with time), and the wobble (the median absolute deviation of each PE from the MDPE).Results:The median (range) values of 14.9% (−21.6%~42.9%) for MDPE, 23.3% (6.9%~62.5%) for MDAPE, −1.9% h−1 (−32.7%~23.0% h−1) for divergence, and 18.9% (4.2%~59.6%) for wobble were obtained from 227 samples from all patients. For the studied population, the PE did not increase with time but with increasing target propofol concentration, particularly following induction.Conclusions:The control of depth of anaesthesia was good in all patients undergoing upper abdominal surgical operation and the predictive performance of the ‘Diprifusor’ target controlled infusion system was considered acceptable for clinical purposes. But the relatively bigger wobble showed that the pharmacokinetic model is not so suitable and requires improvement.
Abstract:Objective:To estimate the impact of autologous transfusion on the status of perioperative immune activation in malignant tumor patients. The Serum Neopterin and Interleukin-2 (IL-2) were measured.Methods:Sixty patients undergoing elective radical resection for malignant stomach tumor were enrolled in the prospective study and assigned to the following groups: (1) Group A received autologous transfusion; (2) Group H received allogeneic transfusion. The perioperative course (Before induction of anesthesia, after operation and 5 d after operation) of Neopterin and IL-2 was compared.Results:In group A, Serum Neopterin was significantly lower than baseline after operation and IL-2 had no significant changes. In group H, both Serum Neopterin and IL-2 were significantly lower than baseline after operation and 5 d after operation. Compared with group A, Serum Neopterin was significantly lower than baseline after operation and 5 d after operation and IL-2 was significantly lower than baseline 5 d after operation.Conclusion:Autologous transfusion decreased the perioperative immune suppression in malignant stomach tumor patients.
Abstract:Objective:To purify Mannan-binding lectin (MBL) from human serum and detect its binding ability to several kinds of bacteria common in infectious diseases of children.Methods:MBL was purified from human serum by affinity chromatography on mannan-Sepharose 4B column. Its binding ability to eight species, 97 strains of bacteria was detected by enzyme-linked lectin assay (ELLA).Results:MBL has different binding ability to bacteria and shows strong binding ability to Klebsiella ornithinolytica and Escherichia coli, but shows relatively lower binding ability to Staphylococcus haemolyticus, Enterobacter cloacae and Staphylococcus epidermidis. To different isolates of Klebsiella pneumoniae, Haemophilus influenzae and Staphylococcus aureus, MBL shows quite different binding ability.Conclusions:MBL has different binding ability to different bacteria, and has relatively stronger binding ability to Gram-negative bacteria. Its binding ability to different isolates of certain kinds of bacteria is quite different.
Abstract:Objective:To observe and evaluate a method that is effective and practical for treatment of cerebral palsied (CP) children in China.Method:The patient’s age and disease type and individual specific conditions were considered in choosing therapy methods accordingly: Chinese herbs, acupuncture, auricular seed pressure, point finger pressing, massage, orthopedic hand manipulation, physiotherapy, occupational therapy, language therapy, etc. Meanwhile we created a new CP treatment model that combines hospitalized treatment with family therapy.Results:The majority of CP patients improved greatly in motor and social adaptation capacities after treatment. Wilcoxon paired rank sum test analysis showed that there were significant differences between the data before and after treatment (P<0.01).Conclusion:This combined therapy method, based on traditional Chinese medicine and western medicine plus family supplemental therapy, is an effective and practical treatment strategy for CP children in China.
Keywords:Traditional Chinese medicine (TCM) combined with western medicine;Therapy;Childhood cerebral palsy
Abstract:Objective:To estimate the oxidative stress and oxidative damage induced by abnormal free radical reactions in IgA nephropathy (IgAN) patients’ bodies.Methods:Seventy-two IgA N patients (IgANP) and 72 healthy adult volunteers (HAV) were enrolled in a random control study design, in which the levels of nitric oxide (NO) in plasma, lipoperoxide (LPO) in plasma and in erythrocytes, and vitamin C (VC), vitamin E (VE) and β-carotene (β-CAR) in plasma as well as the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in erythrocytes were determined with spectrophotometric mothods.Results:Compared with the HAV group, the averages of NO in plasma, and LPO in plasma and in erythrocytes in the IgANP group were significantly increased (P<0.0001), while those of VC, VE and β-CAR in plasma as well as those of SOD, CAT and GPX in erythrocytes in the IgANP group were significantly decreased (P<0.0001). Linear correlation analysis showed that with the increase of the values of NO, and LPO in plasma and in erythrocytes, and with the decrease of those of VC, VE, β-CAR, SOD, CAT and GPX in the IgAN patients, the degree of histological damage of tubulointerstitial regions was increased gradually (P<0.0001); and that with the prolongation of the duration of disease the values of NO, and LPO in plasma and erythrocytes were increased gradually, while those of VC, VE, β-CAR, SOD, CAT and GPX were decreased gradually (P<0.005). The discriminatory correct rates of the above biochemical parameters reflecting oxidative damage of the IgAN patients were 73.8%–92.5%, and the correct rates for the HAV were 70.0%–91.3% when independent discriminant analysis was used; and the correct rate for the IgAN patients was increased to 98.8%, the correct rate for the HAV was increased to 100% when stepwise discriminant analysis was used. The above biochemical parameters’ reliability coefficient (alpha) were used to estimate the oxidative damage of the IgAN patients as 0.8145, the standardized item alpha=0.9730, F=53273.5681, P<0.0001.Conclusions:A series of free radical chain reactions caused serious pathological aggravation in the IgANP’ bodies, thus resulting in oxidative damage in their bodies. In treating IgANP, therefore, it is necessary that suitable dose antioxidants should be supplemented to them so as to alleviate the oxidative damage in their bodies.
Abstract:Thermodynamic parameters of complexation of naphto-15-crown-5 with four alkaline earth ions in aqueous media was determined using titration microcalorimetry at 298.15 K. The stability of the complexes, thermal effect and entropy effect of the complexation is discussed on the basis of the guest ions structure and the solvent effect. The stability constants tendency to vary with ion radius was interpreted. Complex of naphtha-15-crown-5 with calcium ion is very stable due to the synergism of static electric interaction and size selectivity between the host and the guest.
Abstract:The cis and trans isomers separation of 2-butene-1,4-diol and lafutidine were studied by HPLC on two kinds of chiral columns: (S,S)-Whelk-O 1 and ChiraSpher. The isomers of 2-butene-1,4-diol can be separated on both chiral columns while the isomers of lafutidine can only be resolved on ChiraSpher column. The influence of different type and amount of mobile phase modifier on the isomers separation was extensively studied. The resolution of cis and trans isomers of 2-butene-1,4-diol was 2.61 on (S,S)-Whelk-O 1 column with hexane-ethanol (97:3, v/v) as the mobile phase. The resolution of lafutidine was 1.89 on ChiraSpher column with hexane-ethanol-THF-diethylamine (92:3:5:0.1, v/v/v/v) as the mobile phase. LC-MS methods were developed to identify the isomer peaks.