肿瘤细胞免疫治疗单个核细胞采集的护理

目的:探讨肿瘤细胞免疫治疗单个核细胞采集时的护理。方法:收集本院肿瘤生物治疗中心2009年12月～2011年12月收治的1472例患者,在单采室使用德国费森尤斯COM.TEC血分机采血,全程把患者的安全、舒适及采取细胞的质量放于首位,单采和护理进行合理安排、科学操作,获取患者自身外周血单个核细胞60ml,体外分离和单独培养DC和CIK细胞后,用带有虑过网的输血器进行静脉回输。结果:1472例恶性肿瘤患者治疗中有10例(0.006%,10/1472)患者出现手脚、口唇麻木、胸闷心慌等不良反应,及时对症治疗与护理后好转,未出现严重不良反应,采集的细胞的质量均符合实验室标准。结论:肿瘤细胞免疫治疗单个核细胞采集时优质的护理可以保证患者的安全,保证采集的细胞的质量。

Screening serum hepatocellular carcinoma-associated proteins by SELDI-based protein spectrum analysis

AIM： To find out potential serum hepatocellular carcinoma （HCC）-associated proteins with low molecular weight and low abundance 13y SELDI-based serum protein spectra analysis, that will have much application in the diagnosis or differentiated diagnosis of HCC, as well as giving a better understanding of the mechanism of hepato-card nogenesis.METHODS： Total serum samples were collected with informed consent from 81 HCC patients with HBV（＋）/ cirrhosis（＋）, 36 cirrhosis patients and 43 chronic hepatitis B patients. Serum protein fingerprint profiles were first generated by selected WCX2 protein chip capture integrating with SELDI-TOF-MS, then normalized and aligned by Ciphergen SELDI Software 3.1.1 with Biomarker Wizard..Comparative analysis of the intensity of corresponding protein fingerprint peaks in normalized protein spectra, some protein peaks with significant difference between H.CC and cirrhosis or chronic hepatitis B were found.RESULTS： One hundred and twenty-eight serum protein peaks betweeri.2000 and 30000Da were identified under the condition of signal-to-noise 〉 5 and minimum threshold for cluster 〉 20%. Eighty-seven of these proteins were showed significant differences in intensity between HCC and cirrhosis （P 〈 0.05）. Of the above differential proteins, 45 proteins had changes greater than two-fold, including 15 upregulated proteins and 30 downregulated proteins i.n HCC serum. Between HCC and chronic hepatitis B, 9 of 52 differential proteins （P 〈 0.05） had intensities of more than two-fold, including 2 upregulated proteins and 7 downregulated proteins in HCC serum. Between cirrhosis and chronic hepatitis B, 28 of 79 significant differential proteins （P 〈 0.05） changes greater than two-fold in intensity, including 17 upregulated proteins and 11 downregulated proteins in cirrhosis serum. For the analysis of these leading differential proteins in subtraction difference mode among three diseases, the five common downregulated proteins in HCC serum （M/Z 2870, 3941, 2688, 3165, 5483） and two common upregulated proteins （M/Z 3588, 2017） in HCC and cirrhosis serum were screened.CONCLUSION： Because the interference of unspecific secreted proteins from hepatitis B and cirrhosis could be eliminated partly in HCC serum under subtraction difference analysis, these seven common differential proteins have the obvious advantage of specificity for evaluating the pathological state of HCC and might become novel candidate biomarkers in the diagnosis of HCC.

Molecular mechanisms involved in intestinal iron absorption

Iron is an essential trace metal in the human diet due to its obligate role in a number of metabolic processes. In the diet, iron is present in a number of different forms, generally described as haem （from haemoglobin and myoglobin in animal tissue） and non-haem iron （including ferric oxides and salts, ferritin and lactoferrin）. This review describes the molecular mechanisms that co-ordinate the absorption of iron from the diet and its release into the circulation. While many components of the iron transport pathway have been elucidated, a number of key issues still remain to be resolved. Future work in this area will provide a clearer picture regarding the transcellular flux of iron and its regulation by dietary and humoral factors.

Effects of chromium nanoparticle dosage on growth,body composition,serum hormones and tissue chromium in Sprague-Dawley rats

This 6-week study was conducted to evaluate the effects of seven different levels of dietary chromium (Cr) (0,75,150,300,450,600,and 1200 ppb Cr) in the form of Cr nanoparticle (CrNano) on growth,body composition,serum hormones and tissue Cr in Sprague-Dawley (SD) rats. Seventy male SD rats (average initial body weight of (83.2±4.4) g) were randomly assigned to seven dietary treatments (n=10). At the end of the trial,body composition was assessed via dual energy X-ray absorptiometry (DEXA). All rats were then sacrificed to collect samples of blood,organs and tissues for determination of serum hormones and tissue Cr contents. The results indicated that lean body mass was significantly increased (P<0.05) due to the addition of 300 and 450 ppb Cr from CrNano. Supplementation of 150,300,450,and 600 ppb Cr decreased (P<0.05) percent body fat significantly. Average daily gain was increased (P<0.05) by addition of 75,150,and 300 ppb Cr and feed efficiency was increased (P<0.05) by supplementation of 75,300,and 450 ppb Cr. Addition of 300 and 450 ppb Cr decreased (P<0.05) the insulin level in serum greatly. Cr contents in liver and kidney were greatly increased (P<0.05) by the addition of Cr as CrNano in the dosage of from 150 ppb to 1 200 ppb. In addition,Supplementation of 300,450,and 600 ppb Cr significantly increased (P<0.05) Cr content in the hind leg muscle. These results suggest that supplemental CrNano has beneficial effects on growth performance and body composition,and increases tissue Cr concentration in selected muscles.

Inhibitory effects and mechanisms of high molecular-weight phlorotannins from Sargassum thunbergii on ADP-induced platelet aggregation

We evaluated the effects of high molecular-weight phlorotannins from Sargassum thunbergii(STP) on ADP-induced platelet aggregation and arachidonic acid(AA) metabolism in New Zealand white rabbits and Wistar rats.The inhibition of STP on platelet aggregation was investigated using a turbidimetric method,and the levels of the terminal products of AA metabolism were measured using the corresponding kits for maleic dialdehyde(MDA),thromboxane B2(TXB2) and 6-keto-prostaglandin F1α(6-keto-PGF1α) by colorimetry and radioimmunoassay,as appropriate.We found that STP could inhibit ADP-induced platelet aggregation,and the inhibitory ratio was 91.50% at the STP concentration of 4.0 mg/mL.Furthermore,STP markedly affected AA metabolism by decreasing the synthesis of MDA(P<0.01) and increasing the synthesis of 6-keto-PGF1α,thus changing the plasma TXB2/6-keto-PGF1α balance when the platelets were activated(P<0.01).Therefore,STP altered AA metabolism and these findings partly revealed the molecular mechanism by which STP inhibits ADP-induced platelet aggregation.

Mechanism Study of Endothelial Protection and Inhibits Platelet Activation of Low Molecular Weight Fucoidan from Laminaria japonica

Several studies have indicated that fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica could inhibit the activation of platelets directly by reducing the platelet aggregation. To explore the direct effect of LMW fucoidan on the platelet system furthermore and examine the possible mechanism, the endothelial protection and inhibits platelet activation effects of two LMW fucoidan were investigated. In the present study, Endothelial injury model of rats was made by injection of adrenaline(0.4 mg kg-1) and human umbilical vein endothelial cells were cultured. v WF level was be investigated in vivo and in vitro as an important index of endothelial injury. LMW fucoidan could significantly reduce v WF level in vascular endothelial injury rats and also significantly reduce v WF level in vitro. The number of EMPs was be detected as another important index of endothelial injury. The results showed that LMW fucoidan reduced EMPs stimulated by tumor necrosis factor. In this study, it was found that by inhibiting platelet adhesion, LMW fucoidan played a role in anti-thrombosis and the specific mechanism of action is to inhibit the flow of extracellular Ca2+. All in a word, LMW fucoidan could inhibit the activation of platelets indirectly by reducing the concentration of EMPs and v WF, at the same time; LMW fucoidan inhibited the activation of platelets directly by inhibiting the flow of extracellular Ca2+.

The correlation and relationship of obesity and cancer: a possible research perspective

Recently, obesity is a well-recognized risk factor of type 2 diabetes and cardiovascular disease. There is more and more sufficient evidence that excess body weight is an avoidable cause of excess cancers including gastrointestinal, endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal cancers. The mechanism that obesity association with cancer is remains not well understood. There be some most studied hypothesized mechanisms such as, high levels of insulin and free levels of insulin-like growth factors （IGFs）, sex hormones, adipocytokines, intlammatory cytokines, c-Myc （or Myc） oncogenic transcription factor, obesity-induced hypoxia and Warburg effect, and so on. In the future, the potential mechanisms and conclusions in obesity associated with increased risk for developing cancer, and the underlying cellular and molecular mechanisms will be studied.

Molecular mechanism and functional consequences of lansoprazole-mediated heme oxygenase-1 induction

AIM： To investigate the molecular mechanism and functional consequences of heme oxygenase-1 （HO-1） activation by lansoprazole in endothelial cells and macrophages. METHODS： Expression of HO-1 mRNA was analyzed by Northern blotting. Western blotting was used to determine the HO-1 and ferritin protein levels. NADPH-dependent reactive oxygen species （ROS） formation was measured with lucigenin-enhanced chemiluminescence. HO-1 promoter activity in mouse fibroblasts, stably transfected with a 15-kb HO-1 gene that drives expression of the reporter gene luciferase, was assessed usingin vivo bioluminescence imaging. RESULTS： Lansoprazole levels in endothelial cells increased HO-1 mRNA and HO-1 protein levels in macrophages. In addition, lansoprazole-induced ferritin protein levels in both cell systems. Moreover, induction of the antioxidant proteins HO-1 and ferritin by lansoprazole was followed by a decrease in NADPH- mediated ROS formation. The radical scavenging properties of lansoprazole were diminished in the presence of the HO inhibitor, chromium mesoporphyrin IX. Induction of HO-1 gene expression by lansoprazole was not related to oxidative stress or to the activation of the mitogen-activated protein kinase pathway. However, the phosphatidylinositol 3-kinase inhibitor LY294002 showed a concentration-dependent inhibition of HO-1 mRNA and promoter activity.CONCLUSION： Activation of HO-1 and ferritin may account for the gastric protection of lansoprazole and is dependent on a pathway blocked by LY294002.

Effect of Zusanli(ST 36) moxibustion on rat mesenteric microvascular system

OBJECTIVE: To investigate the effect of moxibustion on Zusanli(ST 36) on visceral-mesenteric vesselsbyobservingcirculation.METHODS: Forty-five SD rats were randomly assigned to a moxibustion, electroacupuncture(EA),and blank group. In the moxibustion group, heat stimulation of moxibustion to the Zusanli(ST36)area of normal rats was performed for 15 min. In the EA group, needles were inserted into the Zusanli(ST36)and later alpoint[0.5 cm lateral from Zusanli(ST 36)] for 15 min. The blank group was not given any treatment. We continuously monitored mesenteric microvascular changes with invivo microscopicvideo.RESULTS:Moxibustion and EA to Zusanli(ST 36) increase the diameter of mesenteric arterioles and venules(P<0.05). There were no obvious changes in the blank group. Fine arterial diameter peaked at12 min in the moxibustion group, while it peaked at15 min in the EA group.CONCLUSION:The stimulation of moxibustion and acupuncture to Zusanli(ST 36) has immediate effects on expanding the microvasculature. This dilation may be the mechanism of the gastrointestinal effect of Zusanli(ST36).

Metabolic memory: mechanisms and implications for diabetic vasculopathies

In the past decades,a persistent progression of diabetic vascular complications despite reversal of hyperglycemia has been observed in both experimental and clinical studies.This durable effect of prior hyperglycemia on the initiation and progression of diabetic vasculopathies was defined as"metabolic memory".Subsequently,enhanced glycation of cellular proteins and lipids,sustained oxidative stress,and prolonged inflammation were demonstrated to mediate this phenomenon.Recently,emerging evidence strongly suggests that epigenetic modifications may account for the molecular and phenotypic changes associated with hyperglycemic memory.In this review,we presented an overview on the discovery of metabolic memory,the recent progress in its molecular mechanisms,and the future implications related to its fundamental research and clinical application.

Capillary blood flow in patients with dysmenorrhea treated with acupuncture

OBJECTIVE: To observe capillary blood flow at acupoints during acupuncture treatment of primary dysmenorrhea and gain new insights into its analgesic mechanism. METHODS: Patients with primary dysmenorrhea were enrolled and randomly assigned to a treatment or control group. Subjects' symptoms were differentiated into variousTraditional Chinese Medicine(TCM) syndromes and treated for 10 sessions with puncturing acupuncture or self-pressing right-hand Hegu(LI 4), adding other acupoints based on syndrome. Laser speckle was used to compare the change in the vasomotor amplitude and perfusion of the capillaries in Hegu(LI 4) before and during the treatment. Each subject was required to finish the period pain symptoms observation form, verbal rating scales, numerical rating scale, pain rating index, face rating scale, Zung self-rating depression scale, Zung self-rating anxiety scale, and numerical rating scale before and after treatments. RESULTS: After 10 sessions, the symptom scores, pain index(PI), and visual analog scale(VAS) decreased significantly in treatment group. The volume of blood flow in Hegu(LI 4) declined slightly. No significant evidence supported that needling caused capillary contraction, but the capillary vasomotor amplitude at Hegu(LI 4) increased remarkably. CONCLUSION: Acupuncture can increase the capillary blood flow, thus promoting the flow of Qi and blood in terms of TCM theory, which facilitates pain relief.

Mechanism of herbal pairs with the properties of Qi-tonifying,blood activation,blood-stasis breaking in treating coronary heart disease

OBJECTIVE:To investigating the molecular mechanism of herbal pairs in three types of Chinese medicinals:Qi-tonifying,blood activation,blood-stasis breaking in treatment of coronary heart disease(CHD).METHODS:The components of six herbs were searched in Chinese medicine dictionary and their target proteins were found in PubChem.CHD genes were obtained from PubMed gene database.Ingenuity Pathways Analysis was used to build the pharmacological network of three herbal pairs and CHD molecular network.The canonical pathways between each herbal pair network and CHD network was compared to decipher the molecular mechanism on three herbal pairs in treating CHD.RESULTS:The network analysis showed that there were the common signal pathways of three herbal pairs in treating CHD including hypoxia signaling in the cardiovascular system,Hypoxia-inducible factor 1-alpha signaling,glucocorticoid receptor signaling,G-Protein coupled receptor signaling and pregnane X receptor/retinoid X receptor(PXR/RXR)activation.Further to analyze cardiovascular signaling,cytokine signaling and cytokine signaling,the effective molecules for three herbal pairs in treating CHD included HIF1α and estrogen receptor 1,Qi-tonifying herbal pair included albumin and matrix metallopeptidase 2,and blood-activation herbal pair included estrogen receptor 2 and peroxisome proliferator-activated receptor-γ.CONCLUSION:Each herbal pair can affect some respective CHD-related functions and pathways,meanwhile three herbal pairs exert some mutual effects on CHD-related functions and pathways.Mutual effects of three herbal pairs may be the key components of their total molecular mechanisms and respective effects of each herbal pair may be the characteristic components of their respective molecular mechanism.

Progresses in understanding trauma-induced coagulopathy and the underlying mechanism

Trauma-induced coagulopathy （TIC） is a clinical syndrome caused by imbalance between clotting, anti- coagulation and fibrinolysis resulting from multiple pathological factors such as hemorrhage and tissue injury in the early stage of trauma, and is closely related to the outcome of trauma patients. It is proved in growing evidence that the endogenous coagulation disturbance in trauma itself is the activating factor of TIC, rather than dilution or other acquired coagulopathy. Therefore, a thorough understanding of the molecular mechanisms in the pathogenesis and progression is crucial for effective prevention and treatment in patients with TIC. This review focuses on transitions in the concept of TIC and mechanical progress.

Activation of STAT3 stimulates AHSP expression in K562 cells

Studies on the chaperone protein α-hemoglobin stabilizing protein （AHSP） reveal that abundant AHSP in erythroid cells en-hance the cells＇ tolerance to oxidative stress imposed by excess a-hemoglobin in pathological conditions. However, the poten-tial intracellular modulation of AHSP expression itself in response to oxidative stress is still unknown. The present study ex-amined the effect and molecular mechanism of STAT3, an oxidative regulator, on the expression of AHSP. AHSP expression increased in K562 cells upon cytokine IL-6-induced STAT3 activation and decreased in STAT3 knock-down K562 cells. Reg-ulation of AHSP in oxidative circumstance was then examined in α-globin-overloaded K562 cells, and real-time PCR showed strengthened expression of both AHSP and STAT3. ChIP analysis showed binding of STAT3 to AHSP promoter and binding was significantly augmented with IL6 stimulation and upon α-globin overexpression. Dual luciferase reporter assays of the wildtype and mutated SB3 element, an IL-6RE site, in the AHSP promoter in K562 cells highlighted the direct regulatory ef-fect of STAT3 on AHSP gene. Finally, direct binding of STAT3 to SB3 site of AHSP promoter was confirmed with EMSA as-says. Our work reveals an adaptive AHSP regulation mediated by the redox-sensitive STAT3 signaling pathway, and provides clues to the therapeutic strategy for AHSP enhancement.