Effectiveness of GVHD and GVL of Donor-Derived NK Cell of MHC Haplotype-Mismatched BMT in Mice.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5163-5163
Author(s):  
Chunyan Wang ◽  
Huo Tan ◽  
Guo Kunyuan

Abstract Objective: To study Effectiveness of GVHD and GVL of donor-derived NK cell of MHC haplotype-mismatched BMT in mice. Methods: CB6F1 H-2b/d mice model of EL9611 (H-2d) erythroleukemia was developed by injection of EL9611 (H-2d) cells in tail vein, CB6F1 H-2b/d mice as the recipient, and C57BL/6H-2b mice as the donor. 70 CB6F1 H-2b/d mice were randomly separated into 7 groups (10 mice per group). Control groups (4 groups): the first group was the one without treatment, the second one was simple-irradiation group, the third one was the Ara-c-treated group which Ara-c were injected into mice at 50mg/(kg·one)×6d followed by infusion of EL9611(H-2d) 5 days, the fourth one was haplotype-mismatched GVHD-control group which bone marrow cells and spleen cells of C57BL/6H-2b mice were injected into the mice after 4 hours irradiation. Experimental groups(2 groups): Irradiated 9Gy, mice were injected C57BL/6H-2b NK cells(1×106) and then BM cells after 4 hours in the first experimental group. After irradiation of 9Gy, mice were injected C57BL/6H-2b NK cells(1×106) and then BM cells and spleen cells after 4 hours secondly. The effect was assessed by blood routine test, survival time, body weight, and histopathology in the recipients. Results: [circ1]Life span: the survival time was (10.10±0.88) days, (9.80±0.92)days, (22.70±3.23) days and (20.10±1.73) days in the first, second, third and fifth control groups respectively, (30.10±15.95) days in the fourth control group in which the survival time of 2 mice was more than 30 days. The survival time was (39.10±18.11) days and (49.30±17.24) days in the first and second experimental groups respectively. The survival time in 4 mice of the first experimental group was more than 30 days and 7 mice of the second experimental group. The survival time of the first of experimental group was much longer than that in the first, second, third and fifth control groups (P<0.01). The survival time of the second experimental group was much longer than that in other groups (P<0.05). [circ2]Histopathology change: It was observed that the liver and spleen were enlarged and destroyed in the mice died from leukemia by leukemia cells. [circ3]It was noted that chimerism of Y chromosome appeared in mice of experimental groups of long survival time. Conclusion: The findings provide that donor-derived NK cell has the ability of antileukemia and can reduce GVHD in C57BL/6H-2b→CB6F1 H-2b/d of erythroleukemia mice (EL9611, H-2d).

2021 ◽  

Thermal and massage therapies have long been used to control pain. Although spinal thermal massage (STM) has been used worldwide, its effectiveness has not been proven in a controlled clinical study. We here conducted a non-randomized controlled trial to assess the pain-relieving and immunomodulatory effects of STM in old-aged patients experiencing pain or disability. The experimental group was treated with STM five times a week for 8 weeks and rehabilitative regular care (RRC). The control group was treated with only RRC. Pain and immunological parameters were tested before treatment and after 4 and 8 weeks of treatment. The scores of three pain parameters were lowered by STM, and the differences between the groups were statistically significant at the two time points (p < 0.01). Quality of life determined using the 3-level EuroQol five-dimensional questionnaire scores was significantly higher in patients in the experimental group than those in the control group. Effect sizes (ES) were in the range of medium to large in the pain-related measures (0.54–1.22). The total leukocyte counts and the proportions of lymphocytes and subsets were not significantly different between the groups, whereas the proportions of monocytes and natural killer (NK) cells were higher in the experimental group than in the control group after 8 weeks (p < 0.05). The production of interleukin (IL)-4 and interferon γ in T cells was not significantly different between the groups, whereas the production of IL-2 was high in the control group. However, there was a significant increase in IFN-γ production by NK cells in the experimental group (at 4 weeks, p < 0.05). ES were medium in the immunological measures (0.53–0.68). No significant difference was observed in the production of proinflammatory cytokines, IL-1β, tumor necrosis factor α, or IL-6 between the groups. In conclusion, STM treatment has a positive effect on subjective pain and quality of life. It also enhanced NK cell proportion and activity, suggesting that STM may be beneficial in the prevention of viral diseases and cancer in old-aged people.


2005 ◽  
Vol 284-286 ◽  
pp. 679-682
Author(s):  
J. Kim ◽  
J.K. Ryu ◽  
Min Chul Kim ◽  
Yeon Ung Kim ◽  
Seong Ho Choi ◽  
...  

The purpose of this study was to evaluate the cell affinity of calcium phosphate glass scaffold in the system of CaO-CaF2-P2O5-MgO-ZnO, which is already reported that promoted the bone-like tissue formation in vitro and formed new bone in Sprague-Dawley rats. We prepared calcium phosphate glass saffolds with three-dimensionally interconnected pores of 200~500 µm. Commercial HA scaffold was employed as a control in this study. Bone marrow cells were collected from the healthy human donors and cultured within the prepared scaffolds. After 2, 4, 6, and 8 weeks, hMSCs/scaffold were fixed and stained with hematoxylin and eosin. hMSCs were continuously proliferated both in the experimental and control groups at every incubation period. The number of cells was higher in the experimental group than that of the control group, however, there was no significant difference (p>0.05). Extracellular matrices could be observed at the 2nd and 4th days in the experimental and control groups, respectively. The extracellular matrices were more abundant in the experimental group at all periods. The prepared calcium phosphate glass scaffolds are expected effective in bone tissue engineering.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3747-3747 ◽  
Author(s):  
Rong Fu ◽  
Shaoxue Ding ◽  
Chunyan Liu ◽  
Bingnan Liu ◽  
Hui Liu ◽  
...  

In this study, we intend to detect the expression of TIM3 on peripheral blood NK cells in SAA patients to reveal the further immune pathogenesis of SAA. Furthermore, we tried to further elucidate the changes of functions of TIM3+ NK and TIM3-NK cells in SAA by measuring the functional molecules and cytotoxic activity of TIM3+ NK and TIM3-NK cells. Finally, we observed the therapeutic effects of TIM3 blocker, TIM3+ NK infusion and TIM3-NK infusion on SAA mice model. 1.The TIM3 expression on NK cells in SAA untreated patients was significantly lower than that in SAA remission patients (P<0.05) and normal controls (P<0.01). 2. TIM3-NK cells expressed higher NKG2D and Granzyme B than TIM3+ NK cells in untreated SAA patients. The expression of NKG2A, CD158a and CD158b on TIM3-NK cells were lower than TIM3+ NK cells. 3. The expression of CD80 and CD86 were significantly decreased after being incubated with TIM3-NK and TIM3+NK cells in SAA, especially mDC+ TIM3-NK group, significantly lower than mDC+TIM3+NK group(P<0.01). 4. The apoptosis rate (AR) of K562 cells were significantly increased after being incubated with TIM3-NK and TIM3+ NK cells in SAA, especially K562+TIM3-NK group, significantly higher than K562+TIM3+NK groups(P<0.01). 5. There was no significant difference in the level of AKT of receptor post-signal pathway protein between TIM3-NK and TIM3+ NK cells in patients with SAA, but the level of P-AKT in TIM3-NK cells is higher than TIM3+ NK cells. 6. AA mice model was established. The TIM3 expression on peripheral blood NK cells in SAA mice was significantly lower than that in TBI mice (P<0.05) and normal controls (P<0.05). TIM3-NK cells expressed higher NKG2D than TIM3+ NK cells (P<0.05). The level of P-AKT and PI3K in TIM3-NK cells is higher than TIM3+NK cells. 7. On the 17th day of model establishment, the weight, hemogram and bone marrow cells count of AA mice were significantly lower than that of NC group (p<0.05).The weight, hemogram and bone marrow cells count of CsA treatment group, TIM3+ NK cell infusion treatment group, TIM3-NK cell infusion treatment group, CsA combined with TIM3-NK cell infusion treatment group, CsA combined with TIM3 blocker treatment group has some improvement, TIM3 blocker alone treatment of AA mice slightly increased, the effect is not significant(P>0.05), and combined with CsA has no significant synergistic effect. The therapeutic effect of TIM3-NK cell infusion group was better than that of TIM3+ NK cell infusion group. The therapeutic effect of CsA combined with TIM3-NK cell infusion group was more significant than that of CsA alone group. TIM3-NK cell infusion therapy may have some synergistic effect with CSA. Conclusions 1. In this study, we found that untreated patients with SAA had lower TIM3 expression on NK cells compared with normal controls, andwere correlated with the severity of pancytopenia of SAA. 2. We further confirmed that the expression of activation molecules on TIM3-NK cells was increased and the killing function was enhanced compared with TIM3+NK cells. In addition, TIM3-NK cells have enhanced inhibition of mDCs and K562 cells and play an immunomodulatory role in SAA. Therefore, TIM3 exerts its inhibitory effect on NK cells and participates in the immune pathogenesis of SAA. Low expression of TIM3 contributes to the enhancement of NK cell function, which in turn inhibits the immune activation state of SAA and improves the disease level. 3. The expression of TIM3 on NK cells of AA mice decreased, and the activity of TIM3-NK cells was stronger than that of TIM3+ NK cells, which was consistent with the decrease of TIM3 on NK cells of SAA patients and the strong activity of TIM3-NK cells. After TIM3-NK cell reinfusion, the general condition, blood cell count and bone marrow cell count of SAA mice were improved, and the combined treatment of CsA was more effective. It may further clarify the immune pathogenesis of SAA and provide a new treatment target to improve the efficacy of SAA treatment. Disclosures No relevant conflicts of interest to declare.


Author(s):  
Hasanul Arifin Zul And Masitowarni Siregar

This thesis is focused on the investigation of the effect of applying animal cartoon pictures on students’ achievement in writing narrative text. This study aims to find whether applying animal cartoon pictures significantly affect the students’ writing achievement or not. The data in this study were obtained by administering a written test. The population was the 2015/2016 first year (grade XI) of SMA Swasta Nusantara Lubuk Pakam and 66 students were taken as the sample by using random sampling. The sample was divided into two groups, experimental and control groups. The experimental group was taught by applying animal cartoon pictures while the control group without animal cartoon pictures (x = lecturing). The data were taken the scores from the pre-test and post-test to both experimental and control groups. These data were analyzed by using t-test. The result of computing the t-test obviously showed that t-observed is higher than t-table (5.21 >1,67) with the degree of freedom 64 (df =N-2) at the level significance 0,05 one tail test. It showed that the application of animal cartoon pictures significantly affected the students of SMA Swasta Nusantara Lubuk Pakam achievement in writing narrative text.


Author(s):  
Meryanti Napitupulu And Anni Holila Pulungan

This study was conducted as an attempt to discover the effect of applying Demonstration Method on students’ achievement in speaking skill. It was an experimental research. The subject was students of Grade XII, Vocational High School (Sekolah Menengah Kejuruan: SMK), which consisted of 79 students. The research was divided into two groups: experimental and control groups. The instrument used to collect the data was speaking test. To obtain the reliability of the test, the writer applied Kuder Richardson 21 formula. The result of the reliability was 0.7, and it was found that the test was reliable. The data were analyzed by using t-test formula. The analysis showed that the scores of the students in the experimental group were significantly higher than the scores of the students in the control group at the level of significant m = 0.05 with the degree of freedom (df) 77, t-observed value 8.9 > t-table value 1.99. The findings indicate that using Demonstration Method significantly affected the students’ achievement in speaking skill. So, English teachers are suggested to use Demonstration Method in order to improve students’ achievement in speaking skill.


2021 ◽  
pp. 104973152110014
Author(s):  
Siu-ming To ◽  
Xiaoyu Liu

Purpose: Using a nonrandomized control group pretest–posttest assessment, this study aimed to examine the outcomes of community-based youth empowerment initiatives that were informed by design thinking. Method: A total of 553 youth living in Hong Kong were recruited to participate in this study. Among them, 213 youth self-selected to join the experimental group, and 340 youth joined the two control groups. Multivariate analysis of covariance and post hoc group comparisons were used to examine the differences among the three groups at the posttest assessment. Results: The results indicate a positive improvement in creative self-efficacy among participants of the experimental group compared to the two control groups. Significant differences were also found between the experimental group and the second control group in terms of youth–adult partnerships and youth empowerment in the community. Conclusion: Youth empowerment programs informed by design thinking may reinforce self-efficacy beliefs by encouraging youth to bring about innovations in their community.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yan Feng ◽  
Hui Zhao ◽  
Fu-Dong Shi ◽  
Weina Jin

Objectives: To screen miRNA profile of peripheral NK cells in ischemic stroke mouse model and investigate a most promising candidate (miR-1224) for post-transcriptional regulation of NK cell function after ischemic stroke. Methods: Mice were subjected to a 60 min focal cerebral ischemia produced by transient intraluminal occlusion of MCAO. For NK cell isolation, cell suspensions from the spleens after reperfusion were enriched for NK cells using magnetic-bead sorting system after staining with anti-NK1.1 microbeads. The nCounter Mouse miRNA array was used to analyze miRNA expression profile in splenic NK cells over the time course of experimental ischemic stroke. Based on the miRNA data, we further in vitro modulated miR-1224 in NK cells using mimics or inhibitor, then injected i.v into Rag2-/-γc-/- recipient mice. Neurological function score was compared and spontaneous infection was assessed by pulmonary bacteria colony culture, and changes in potential signaling pathway (SP1/TNF-α) were verified by rt-PCR and western blot. Results: Through miRNA expression profile analysis, we have identified significant changes at each time point in peripheral NK cells after cerebral ischemia. Among all screened miRNA, miR-1224 remarkably increased in MCAO group, which was verified by PCR. Then isolated NK cells treated with mimics or inhibitors, were transferred to Rag2-/-γc-/- recipient mice. Compared with WT mice, Rag2-/-γc-/- mice with miR-1224 inhibitor exhibited increased NK cell number, enhanced NK cell activation/cytotoxicity feature, as well as better neurological behaviors and reduced pulmonary infection after MCAO. Moreover, compared with the control group, NK cells with miR-1224 inhibitor showed significantly increased SP1 gene and protein phosphorylation. As SP1 gene is one of the potential targets of miR-1224, this study suggests that miR-1224 may regulate NK cell function after MCAO, which is associated with SP1 pathway. Conclusion: The miRNA profiling of splenic NK cells provided insight into the functional mechanism and signaling pathways underlying the distinct organ-specific NK cell properties, which will contribute to the better understanding of NK cell mediated immune-response in relation to different stages of stroke.


2018 ◽  
Vol 40 (01) ◽  
pp. 62-70 ◽  
Author(s):  
Alexander Schenk ◽  
Walter Pulverer ◽  
Christine Koliamitra ◽  
Claus Bauer ◽  
Suzana Ilic ◽  
...  

AbstractPositive effects of exercise on cancer prevention and progression have been proposed to be mediated by stimulating natural killer (NK) cells. Because NK cell receptors are regulated by epigenetic modifications, we investigated whether acute aerobic exercise and training change promoter DNA methylation and gene expression of the activating KIR2DS4 and the inhibiting KIR3DL1 gene. Sixteen healthy women (50–60 years) performed a graded exercise test (GXT) and were randomized into either a passive control group or an intervention group performing a four-week endurance exercise intervention. Blood samples (pre-, post-GXT and post-training) were used for isolation of DNA/RNA of NK cells to assess DNA promoter methylation by targeted deep-amplicon sequencing and gene expression by qRT-PCR. Potential changes in NK cell subsets were determined by flow cytometry. Acute and chronic exercise did not provoke significant alterations of NK cell proportions. Promoter methylation decreased and gene expression increased for KIR2DS4 after acute exercise. A high gene expression correlated with a low methylation of CpGs that were altered by acute exercise. Chronic exercise resulted in a minor decrease of DNA methylation and did not alter gene expression. Acute exercise provokes epigenetic modifications, affecting the balance between the activating KIR2DS4 and the inhibiting KIR3DL1, with potential benefits on NK cell function.


1970 ◽  
Vol 7 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Md Sharif Hossain ◽  
Fatema Begum

In Bangladesh some researchers have done several studies to find the correlation of simple diffuse goiter with arsenic level but no one conducted any study to find the differences of urinary iodine, urinary arsenic, radioiodine uptake, the thyroid stimulating hormone (TSH) and free thyroxin (FT4) levels between goitrous and non goitrous. That is why, in this research an attempt has been made to compare the urinary iodine, urinary arsenic, radioiodine uptake, TSH and FT4 levels between experimental group with simple diffuse goiter and healthy control group. In this study another purpose has also been made to find the associations between different pairs of variables for both experimental and control group. In this study we have tried to find the impacts of arsenic level on simple diffuse goiter. This is a case-control analytical study. The study is carried out in the Institute of Nuclear Medicine and Ultrasound, in collaboration with the thyroid out patient department of Bangabandhu Sheikh Mujib Medical University. A total of eighty five (85) subjects are included in the study. Among the 85 subjects, a sample of forty five is considered for experimental group with simple diffuse goiter and another sample of forty is considered for healthy control group without any thyroid disease. From the experimental results it has been found that, the arsenic levels, FT4 and radioiodine uptake levels at 2 hours between the experimental and control groups are significantly different but the urinary iodine levels, TSH levels and radioiodine uptake levels at 24 hours between the experimental and control groups are not statistically different. From the experimental results it has also been found that there is significant differentiation between experimental and controls groups in respect of association between different pairs of variables. In this study, another significant finding is that iodine deficiency is not only the factor of causing simple diffuse goiter, but arsenic level is also one of the most important factor of causing simple diffuse goiter. Key words: Iodine deficiency, Simple diffuse goiter, Urinary arsenic, Statistical analysis, Association, Experimental and Control groups  DOI = 10.3329/dujps.v7i1.1224 Dhaka Univ. J. Pharm. Sci. 7(1): 89-98, 2008 (June)


2017 ◽  
Vol 13 (1) ◽  
pp. 39
Author(s):  
Duriye Esra Angın

The purpose of this research is to investigate the effects of Dora the Explorer cartoon on the spatial concept acquisitions and spatial abilities of the preschool children. The study was carried out with 80, 60-71 month old children attending preschools. Post-test only control group model is used in the research in order to identify the existing phenomena in a controlled manner. “The Bracken Basic Concept Scale, Third Edition: Receptive (BBCSIII:R) Form Direction/Position Subscale” and two different “Spatial Ability Games” were used to assess children’s spatial concept acquisitions and spatial abilities. Independent sample t-test was used in order to compare the average of post-test scores of the children in the experimental and control groups. According to the findings, it is found that there is meaningful difference between scores of post-tests of direction/position subscale and spatial ability games score. Comparing the scores of post-test of direction/position subscale and spatial ability games of experimental and control groups, it was found that there was a meaningful differentiation in favor of experimental group.


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