TFAR19 is a novel apoptosis-related gene and can accelerate cell apoptosis in the presence of apoptosis inducements. Here, we studied the effects of TFAR19 on some biophysical properties of mouse erythroleukemia (MEL) cells and their molecular and structural basis. After transfected with TFAR19 and apoptosis inducement, MEL revealed a high cell membrane fluidity, a decrease in resynthesis of phospholipids, an increase in the proteins/nucleic acids ratio, a relatively orderly cytoskeleton network, an impaired deformability, a low integrin aM expression, and a decrease in adhesion to endothelial cells. These findings suggest the potential of TFAR19 for antitumor cell migration, and thus for antitumor gene therapy.
Transcutaneous electrical nerve stimulation (TENS) has been shown to be an effective measure for pain relief The aim of the present study was to determine the optimal intensity and interval of repeated 100 Hz TENS for the treatment of chronic inflammatory hyperalgesia in a monoarthritic pain model of the rat, and to assess the changes of the spinal substance P (SP) release in response to TENS treatment. A reliable, reproducible chronic monoarthritic pain model was produced by intra-articular injection of complete Freund's adjuvant (CFA) at single ankle joint. The efficacy of 100 Hz TENS treatments with different frequencies and intensities was compared. In the acute period (within 3 weeks) of monoarthritis, twice-a-week schedule of TENS reduced the swelling of the inflamed ankle significantly. In the stable period (4-9 weeks), however, once-a-week schedule produced a significantly better therapeutic effect on both inflammation and arthritic hyperalgesia than that of twice- or five-times-a-week schedule. Using three levels of intensity of TENS, we found that the weaker (1-1-2 mA) stimulation produced significantly better therapeutic effects. Repeated TENS produced a reduction of SP content in spinal perfusate in parallel with the progressive reduction of the arthritic pain scores. Our results suggest that (i) consecutive TENS treatments produced cumulative effect for chronic hyperalgesia, (ii) for chronic inflammatory hyperalgesia, a weaker intensity and more sparsely arranged treatment schedule may produce better therapeutic effect and (iii) a decrease in SP release may serve as one of the possible neurochemical mechanisms underlying the therapeutic effects of multiple TENS treatments on chronic inflammatory hyperalgesia.
TRAIL can selectively induce rapid apoptosis of various types of tumor cells. We induced the expression of TRAIL in Jurkat cells, and measured the adhesion of cells to human umbilical vein endothelial cells (HUVECs) and laminin (LN) in a parallel plate flow chamber system and by using a colorimetric method. The apoptosis percentage, cycle distribution, intracellular Ca(2+) concentration, and adhesion molecule expression of the cells were detected by flow cytometry. Cytoskeleton was observed with a laser confocal microscopy. The roles of adhesion molecules in the cell interaction was defined by their function blocking. The results showed that TRAIL attenuated the adhesion of Jurkat cells to HUVECs and LN, as well as their transendothelial migration. The increased apoptosis and G1-phase cell percentages, decreased intracellular Ca(2+) concentration, depolymerized actin and impaired cell deformability could contribute to the decreased adhesion of Jurkat cells caused by TRAIL. Furthermore, CD11a was found to play a more important role than CD62L in the adhesion of Jurkat cells to HUVECs. These findings contribute to the knowledge on the role of TRAIL in tumor metastasis and provide mechanistic basis for the clinical application of TRAIL and tumor therapy.
We investigated the biomechanical properties of reticulocytes obtained from an animal model of hemolytic anemia induced by antibody injection. The hemorheological indices, membrane viscoelasticity, membrane fluidity, and the secondary structure of membrane proteins of the reticulocytes were monitored continuously during the course of their maturation into erythrocytes. The results indicate that reticulocytes had lower deformability, lower membrane fluidity, greater viscoelastic modulus and lesser proportions of α-helices and β-sheets in protein secondary structures than mature erythrocytes. All these indices approached to the level of normal erythrocytes when reticulocytes transformed during maturation. The results help to enhance our understanding of the biomechanical properties of the reticulocytes in their maturing process with clinical diagnosis significances.
Dendritic cells (DCs), which are the most efficient antigen-presenting cells (APCs) currently known, can be derived from CD14+ monocytes (DC predecessor cells) in vitro. Immature DCs actively take up antigens and pathogens, generate major histocompatability complex-peptide complexes, and migrate from the sites of antigen acquisition to secondary lymphoid organs to become mature dendritic cells that interact with and stimulate T-lymphocytes. During this process, the cells must undergo deformation to translocate through several barriers, including the basement membrane and interstitial connective tissue in the blood vessel wall. To further understand the mechanisms of the activation of immunological responses and the migration from peripheral tissue to secondary lymphoid organs, we have applied biophysical and microrheological methods to study the development processes of DCs in vitro. The results showed that membrane fluidity, osmotic fragility, membrane viscoelastic properties, infrared spectroscopy, and cytoskeleton organization of DCs exhibit significant differences in different developmental stages.
Blood cells, mainly including red blood cells, white cells and platelets, undergo their differentiating processes when they perform their physiological functions, which accompany the changes of cell rheological chacteristics. This paper reviews the recent progresses in rheological study on the differentiating blood cells, which broaden the research on rheology and biophysics.
The purpose of this study was to examine the effects of Compound Dan-shen Root Dropping Pill (CDRDP) (Tasly Group, Tianjing, China) on hemorheology and biorheology of dogs suffering from hyperlipidemia induced by high-fat diet. Eighteen dogs were randomly divided into two groups: the high-fat diet group (H group); the control group (C group), fed with a standard laboratory diet. Six month later, six dogs in the H group were chosen as the drug-taking group (D group), to which CDRDP was administered, fed with the same diet as H group. In the 4th month, blood was taken from the veins of the dogs, and blood triglyceride (TG), total cholesterol (TC), RBC hemorheological indexes as well as malondialdehyde (MDA), glutathione transferase (GSH-ST) and superoxide dismutase (SOD) activities in plasma and erythrocytes were measured. Compared with H group, TC, TG, plasma MDA levels, the whole blood viscosity, RBC osmotic fragility and the value of CHOL (cholesterol)/PL (phospholipid) of the membrane of D group decreased, however, erythrocyte GSH-ST, histopathological changes in liver, deformation index (DI), orientation index (DI)(or), small deformation index (DI)(d), electrophoresis ratio and microfluidity of the membrane lipid bilayer of RBCs, increased distinctly. CDRDP can improve micro-hemorheological characteristics, therefore has a significant therapy application of hyperlipidemia.
Dendritic cells (DC) are sentinels of the immune system. They and their precursors undergo complex migration to perform their function in vivo. Binding of DC to vascular endothelial cells in a flow field has not been investigated. We therefore determined adhesion of DC and their precursors, MO, to human umbilical vein endothelial cells (HUVECs) under various shear stresses by using a flow chamber system. The results showed that the binding was reduced with developmental stages of DC, which partially depended on CD11a and cell surface charges. The data had potential relevance for anti-cancer immunotherapy strategies favoring the application of mDC.
Using μ-opioid receptor knockout (MKO) mice, we examined ethanol-induced FOS immunoreactivity (FOSir) in the brain as an indicator of neuronal activation to assess the role of the μ-opioid receptor in modulating ethanol's actions in the central nervous system (CNS). Saline stimulated FOSir in the paraventricular thalamic nucleus (PVA) and the dorsal hypothalamic area (DA) in MKO mice, but not in wild-type (WT), suggesting that MKO homozygotes may differ responsively from WT. Treatment with ethanol (4g/kg, i.p.) induced FOSir in the PVA, DA, supraoptic (SO), paraventricular hypothalamic (PVN), lateral parabrachial (LPB), locus coeruleus (LC) and Edinger–Westphal (EW) nuclei in both MKO and WT mice. However, ethanol stimulated modest FOSir in the lateral septal division (LSV), suprachiasmatic nucleus (SCh) and the dorsal and ventral lateral geniculate nuclei (DLG and VLG) in WT mice, but not in MKO mice. In contrast, higher levels of ethanol-induced FOSir were observed in the ventral pallidum (VP) and globus pallidus (GP) of MKO mice as compared to WT. These data suggest that ethanol continues to activate several brain regions, even without the μ-opioid receptor pathway. However, the μ-opioid receptor may be significant in mediating ethanol's effects in some restricted areas of the brain.
Objective To study the effects of a new device of brain protection-carotid artery filtrum on hemorheological properties of carotidartery blood.Methods China mini-pigs,whose carotid artery blood flow is similar to that of human were selected as the animal model.After the filtrum was placed in the carotid artery,hemorheological parameters of blood at both far and near end of carotid artery were measured by a ektacytometer.Results The results showed that significant differences of hemorheological parameters were found between the two ends of the carotid artery,which illuminates that the new device,carotid artery filtrum can definitely protect brain.
Objective To study the characteristicts of hemorheology and free radical metabolism of workers at plateau and to observe the protective effects of Luzhibao.Methods The healthy workers from outback plain were randomly divided into 3 groups:plain,plateau and Luzhibao group.The blood HCT,viscosity,deformation index(DI),MDA,SOD,CAT,GSH-Px were determined.Results Compared with plain group,MDA,CAT and GSH-Px levels of plateau group increased,and DI decreased significantly.The harmful influences could be reduced by Luzhibao.Conclusion Luzhibao is potent to remove free radical,improve hemorheological properties,strengthen body ability against hypoxia and protect the body from harm induced by plateau.
The cDNA fragment of human TRAIL (TNF-related apoptosis inducing ligand) was cloned into RevTet-On, a Tet-regulated and high-level gene expression system. The gene expression system was constructed in a human leukemic cell line: Jurkat. By using RevTet-On TRAIL gene expression system in Jurkat as a cell model, we studied the influence of TRAIL gene on the changes of cellular apoptosis before and after the TRAIL gene expression, which was induced by adding tetracycline derivative doxycycline (Dox). The results indicated that the cellular apoptosis ratio was largely dependent on the trail gene expression level. Moreover, it was found that the apoptosis-inducing TRAIL could cause significant changes in the biophysical properties of Jurkat cells. The cell surface charge density decreased, the membrane fluidity declined, the elastic coefficients K1 increased, and the proportion of a-helix in membrane protein secondary structure decreased. Thus, the apoptosis-inducing TRAIL gene caused significant changes on the biomechanic properties of Jurkat cells.
在建立一种可靠的慢性炎症痛动物模型的基础上,用不同间隔的经皮神经电刺激(TENS)给予治疗,对其疗效进行比较观察,找出较适宜的TENS间隔时间.结果:多次刺激之间的间隔时间是影响多次TENS治疗慢性炎症痛的重要因素.在单发性关节炎发病的不同时期,治疗的适宜间隔时间有所不同.急性期(1~3周),每周2次效果最优;而在稳定的慢性迁延期(4~9周)内,每周1次较好.