scholarly journals Intratracheal administration of bone marrow c-kit+ cells offered hopes in ameliorating asthmatic pathologies via the control of miRNA-133 and -126

2020 ◽  
Author(s):  
Reza Rahbarghazi ◽  
Rana Keyhanmanesh ◽  
Fatemeh Mirershadi ◽  
Hossain Heiran ◽  
Hesam Saghaei Bagheri ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Serum Levels ◽  
Male Rats ◽  
Pathological Examination ◽  
Pcr Analysis ◽  
Control Group ◽  
Intratracheal Administration ◽  
Therapeutic Outcomes ◽  
Mirnas Expression

Abstract Background There are still challenges regarding c-kit+ cells therapeutic outcome in the clinical setting. Here, we examined of c-kit+ cells effect on the alleviation of asthma by modulating miRNAs expression.MethodsTo induce asthma, male rats were exposed to ovalbumin. Bone marrow-derived c-kit+ cells were enriched by MACS. Animals were classified into four groups (each in 6 rats). Control rats received PBS intratracheally; Ovalbumin-sensitized rats received PBS intratracheally; Ovalbumin-sensitized rats received PBS intratracheally containing 3×105 c-kit+ and c-kit- cells. Cells were stained with Dil fluorescent dye to track in vivo condition. Pathological changes were monitored in asthmatic rats after transplantation of c-kit+ and c-kit- cells. Serum levels of IL-4 and INF-γ were measured by ELISA. Transcription of miRNAs (-126 and 133) were assessed by real-time PCR analysis.ResultsPathological examination, Th1 and Th2 associated cytokines fluctuation confirmed the occurrence of asthma in rats indicated by chronic changes and prominent inflammation compared to the control group (p<0.05). Both c-kit+ and c-kit- cells were verified in pulmonary niche. Administration of c-kit positive cells had potential to changes INF-γ/IL-4 ratio and closed to the normal values compared to matched-control asthmatic rats (p<0.05). We also found that c-kit+ cells regulated the expression of miRNA-126 and -133, indicated by increase of miRNA-133 and decrease of miRNA-126 compared to cell-free sensitized groups (p<0.05). c-kit- cells were unable to promote any therapeutic outcomes in asthmatic milieu.ConclusionsIn overall, c-kit+ cells had potential to diminish asthma-related pathologies presumably by controlling the transcription of miRNA-126 and -133.

Abstract 17100: Priming with Erythropoietin Enhances Survival and Pro-Angiogenic Properties in Mesenchymal Stem Cells

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Takuya Mizukami ◽  
Yoshitaka Iso ◽  
Haruka Usui ◽  
Chisato Sato ◽  
Masahiro Sasai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Histological Study ◽  
Blood Perfusion ◽  
Pcr Analysis ◽  
Control Group ◽  
Erythroid Progenitors ◽  
Epo Receptor

Introduction: Accumulating evidence from animal studies shows that the administration of mesenchymal stem cells (MSCs) from bone marrow ameliorates tissue damage after ischemic injury. However, the inability to effectively graft culture-expanded stem cells to diseased or injured tissues remains a challenge for cell therapy. Erythropoietin (Epo) is an erythropoiesis-stimulating cytokine and protects erythroid progenitors from cell death. Epo receptor was identified in MSCs, but the action of Epo/Epo receptor signaling is not determined. In the present study we investigated whether Epo enhanced the survival and pro-angiogenic potential in the MCSs in both culture and animal experiments. Methods and Results: Epo receptor was expressed on MSCs isolated from bone marrow in GFP-transgenic rats. In culture study, the Epo treatment (80IU/ml) significantly propagated the MSCs compared with the controls (2-fold increase, p<0.05). Quantitative RT-PCR analysis demonstrated that Epo significantly enhanced the expressions of basic-fibroblast growth factor and stromal cell-derived factor-1 in the cultured MSCs. In vivo, the GFP-MSCs preconditioned with and without Epo (80IU/ml) for 48 hours were locally administered to rat hindlimb ischemia model (n=11 in each group). Priming with Epo significantly increased the MSC engraftment in perivascular area of the injured muscle at day 3 after the implantation more than without Epo (1.5±1.3 vs. 3.0±2.1, p<0.05). The MSCs preconditioned with Epo significantly promoted blood perfusion documented by laser Doppler and capillary growth in histological study compared with the control group at day 14 (p<0.05, respectively). In addition to promoting neovascularization, the MSCs with Epo significantly inhibited macrophage infiltration in perivascular are (p<0.05 vs. the control). Conclusions: Epo induced the proliferative activity and enhanced the production of angiogenic cytokines in the cultured MSCs from bone marrow. In vivo study demonstrated that the short-term priming with Epo promoted the cellular engraftment and neovascularization in the MSC therapy for ischemic limb muscle. MSC implantation combined with Epo may be a novel and feasible strategy in therapeutic angiogeneis.

scholarly journals Evaluation of inflammatory miRNA155 and 146a expression in heart tissue of ovalbumin-sensitized male rats

2021 ◽  
Vol 9 (1) ◽  
pp. 11-11
Author(s):  
Mehdi Hassanpour ◽  
Akbar Darbin ◽  
Rana Keyhanmanesh ◽  
Mahdi Ahmadi ◽  
Reza Rahbarghazi
Keyword(s):  
Cardiac Tissue ◽  
Serum Levels ◽  
Field Analysis ◽  
Male Rats ◽  
Inflammatory Factors ◽  
Pcr Analysis ◽  
System Response ◽  
Control Group ◽  
Pathological Changes ◽  
Pulmonary Tissue

Introduction: Asthma is a chronic pulmonary inflammation occurred in response to different allergens, leading to respiratory system insufficiency. The production of different inflammatory factors and enhanced immune system response may affect the function of other organs. The aim of this study was to investigate the expression of inflammatory microRNAs in cardiac tissue in asthmatic rat model. Methods: In this study, the animals were allocated into Control and Asthmatic rats (n=8). To induce asthma, rats were challenged with ovalbumin. 14 days after induction of asthma, rats were euthanized and Hematoxylin-Eosin staining was performed to assess pathological changes in pulmonary tissue. Serum levels of cardiac enzymes were measured using ELISA kits. Finally, transcription level of inflammatory miRNAs, miRNA-146a and -155, were measured using real-time PCR analysis. Results: Based on our findings, histological examination indicated the existence of pathological changes in pulmonary tissue after asthma induction. Bright-field analysis revealed an existence of inflammatory response and cytotoxicity in cardiac tissue. Also, the serum levels of CpK-MB, ALT, and AST were significantly higher in the serum of asthmatic group compared to control group (p<0.05). Finally, asthmatic condition induced the expression of (2-fold) miRNA-146a and (1.5-fold)-155 in cardiac tissue, respectively. Conclusion: As a conclusion, it could be concluded that asthmatic condition induces systemic inflammation in cardiac tissue. On a more general note, we propose that therapeutical approaches directed to inflammatory pathway may be required to preserve cardiac injuries caused of asthma.

DPP IV inhibitor treatment attenuates bone loss and improves mechanical bone strength in male diabetic rats

2014 ◽  
Vol 307 (5) ◽  
pp. E447-E455 ◽  
Author(s):  
Lorenzo Glorie ◽  
Geert J. Behets ◽  
Lesley Baerts ◽  
Ingrid De Meester ◽  
Patrick C. D'Haese ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Strength ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Bending Test ◽  
Control Group ◽  
Mechanical Resistance ◽  
Three Point Bending ◽  
Dpp Iv

Dipeptidyl peptidase IV (DPP IV) modulates protein activity by removing dipeptides. DPP IV inhibitors are currently used to improve glucose tolerance in type 2 diabetes patients. DPP IV substrates not only increase insulin secretion but also affect bone metabolism. In this study, the effect of DPP IV inhibitor sitagliptin on bone was evaluated in normal and streptozotocin-induced diabetic rats. This study included 64 male Wistar rats divided into four groups ( n = 16): two diabetic and two control groups. One diabetic and one control group received sitagliptin through drinking water. Tibiae were scanned every 3 wk using an in vivo μCT scanner. After 6 and 12 wk, rats were euthanized for histomorphometric analysis of bone parameters. The mechanical resistance of femora to fracture was assessed using a three-point bending test, and serum levels of bone metabolic markers were measured. Efficient DPP IV inhibition was achieved in sitagliptin-treated groups. Trabecular bone loss, the decrease in trabecular number, and the increase in trabecular spacing was attenuated through sitagliptin treatment in diabetic rats, as shown by in vivo μCT. Bone histomorphometry was in line with these results. μCT analysis furthermore showed that sitagliptin prevented cortical bone growth stagnation in diabetic rats, resulting in stronger femora during three-point bending. Finally, the serum levels of the resorption marker CTX-I were significantly lower in sitagliptin-treated diabetic animals compared with untreated diabetic animals. In conclusion, sitagliptin treatment attenuates bone loss and increases bone strength in diabetic rats probably through the reduction of bone resorption and independent of glycemic management.

scholarly journals Investigation Into Effect Of Crude Mixture Of Abrus Precatorius Seed On Hypothalamopituitary Gonadal Axis And Development Of Antifertility In Male Rats

1970 ◽  
Vol 36 (1) ◽  
pp. 103-109 ◽  
Author(s):  
S Talukder ◽  
MA Hossain ◽  
S Sarker ◽  
MAH Khan
Keyword(s):  
Negative Impact ◽  
Sperm Count ◽  
Sharp Decrease ◽  
Serum Levels ◽  
Serum Biochemistry ◽  
Male Rats ◽  
Male Rat ◽  
Control Group ◽  
Abrus Precatorius ◽  
Crude Mixture

To evaluate the antifertility effect of crude mixture of A. precatorius seeds at the dose level of 50 mg/kg body weight in adult male rats, after oral administration to male rats for 40 days, the rats were sacrificed and hormonal profiles, serum biochemistry, sperm count and histological changes were recorded. A sharp decrease in the serum levels of testosterone (0.70 ± 0.17 ng/ml), FSH (0.70 ± 0.22 lU/L), and LH (0.87 ± 0.35 IU/L) was detected compared to control (FSH, LH and testosterone levels 0.93 ± 0.15 ng/ml, 0.76 ± 0.28 IU/L, 1.44 ± .011 IU/L, respectively). A significant reduction of epididymal sperm count (2.34 million/mL) was noted in treated rats as compared to control group (7.87 million/mL). Histology of testes showed marked atrophy of the testes, which was characterized by disruption of the seminiferous epithelium and atrophy of the Leydig cells. Crude mixture of A. precatorius seed has a negative impact on male reproductive functions. It might be suggested that crude mixture of A. precatorius seeds might have antifertility property for male rats.   Keywords: Abrus precatorius; antifertility; male rat; testosterone. DOI: http://dx.doi.org/10.3329/bjar.v36i1.9234 BJAR 2011; 36(1): 103-109

scholarly journals Shortened platelet half-life in multiple myeloma

Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 514-520
Author(s):  
E Fritz ◽  
H Ludwig ◽  
W Scheithauer ◽  
H Sinzinger
Keyword(s):  
Multiple Myeloma ◽  
Half Life ◽  
Serum Levels ◽  
Statistical Correlation ◽  
Control Group ◽  
Healthy Controls ◽  
Platelet Factor ◽  
Healthy Control

Various defects in platelet function have been reported as being associated with multiple myeloma. In 30 myeloma patients and 15 healthy controls, we investigated platelet survival using in vitro labeling of autologous platelets with 111indium-oxine and measuring the in vivo kinetics of the radioisotope. Significantly shortened platelet half- life in patients averaged 73 hours, while platelet half-life in the healthy controls averaged 107 hours. In myeloma patients, serum levels of thromboxane B2, beta-thromboglobulin, and platelet factor 4 were significantly elevated; aggregation indices were within the pathological range; platelet counts and spleen-liver indices, however, were comparable to those of the healthy control group. No statistical correlation was found between platelet half-life and paraprotein concentrations. Our findings suggest an initial--so far unexplained-- intravascular process of platelet activation and consumption that finally manifests in shortened platelet half-life. It seems that overt thrombocytopenia develops only when the compensatory capacity of the bone marrow finally becomes exhausted. Further studies should be able to elucidate the pathophysiologic processes involved.

scholarly journals Early megakaryocyte lineage-committed progenitors in adult mouse bone marrow

2021 ◽  
Author(s):  
Zixian Liu ◽  
Jinhong Wang ◽  
Miner Xie ◽  
Peng Wu ◽  
Yao Ma ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Single Cell ◽  
Pcr Analysis ◽  
Mouse Bone Marrow ◽  
Hematopoietic Stem ◽  
Colony Assay ◽  
Megakaryocyte Progenitors ◽  
Cell Colony

Hematopoietic stem cells (HSCs) have been considered to progressively lose their self-renewal and differentiation potentials prior to the commitment to each blood lineage. However, recent studies have suggested that megakaryocyte progenitors are generated at the level of HSCs. In this study, we newly identified early megakaryocyte lineage-committed progenitors (MgPs) in CD201-CD48- cells and CD48+ cells separated from the CD150+CD34-Kit+Sca-1+Lin- HSC population of the bone marrow in C57BL/6 mice. Single-cell transplantation and single-cell colony assay showed that MgPs, unlike platelet-biased HSCs, had little repopulating potential in vivo, but formed larger megakaryocyte colonies in vitro (on average eight megakaryocytes per colony) than did previously reported megakaryocyte progenitors (MkPs). Single-cell RNA-sequencing supported that these MgPs lie between HSCs and MkPs along the megakaryocyte differentiation pathway. Single-cell colony assay and single-cell RT-PCR analysis suggested the coexpression of CD41 and Pf4 is associated with megakaryocyte colony-forming activity. Single-cell colony assay of a small number of cells generated from single HSCs in culture suggested that MgPs are not direct progeny of HSCs. In this study, we propose a differentiation model in which HSCs give rise to MkPs through MgPs.

scholarly journals Genotoxic evaluation of ceftriaxone by in vivo micronucleus test in albino mice

2018 ◽  
Vol 7 (9) ◽  
pp. 1705
Author(s):  
Kunjumon Dayana ◽  
Megaravalli R. Manasa
Keyword(s):  
Bone Marrow ◽  
Micronucleus Test ◽  
Micronucleus Assay ◽  
Generation Cephalosporin ◽  
New Drugs ◽  
Control Group ◽  
Genotoxic Potential ◽  
Polychromatic Erythrocytes ◽  
Albino Mice

Background: Genotoxicity screening of drugs is essential. It is mandatory for new drugs. However, screening of drugs already in use is also necessary. Several cephalosporins are reported to induce chromosomal aberrations in previous studies. But there is paucity of data regarding the genotoxic potential of ceftriaxone. Hence the present study was undertaken to evaluate the genotoxic potential of ceftriaxone, a third generation cephalosporin, by micronucleus assay in albino mice.Methods: In vivo micronucleus test was performed with mice bone marrow after intraperitoneal injection of ceftriaxone at 100mg/kg BW and 200mg/kg BW at 24 hr and 48 hr harvest time. Mice bone marrow was harvested, and slides were prepared. The percentage of micronucleated polychromatic erythrocytes (% MnPCE) and the ratio of polychromatic erythrocytes to normochromatic erythrocytes (PCE:NCE) were determined. The data from ceftriaxone treated groups was compared with control group and analyzed using ANOVA followed by Dunnett's test.Results: Ceftriaxone at the dose of 100mg/kg BW and 200mg/kg BW did not exhibit any significant increase in the percentage of micronucleated polychromatic erythrocytes. It also did not decrease the ratio of polychromatic erythrocytes to normochromatic erythrocytes significantly.Conclusions: The present study demonstrates that ceftriaxone is not genotoxic in in vivo micronucleus study in albino mice at a dose of 100mg/kg BW and 200mg/kg BW.

Study on mechanism of Tim-3 on immune escape in benzene-induced acute myeloid leukemia

2020 ◽  
Author(s):  
qiong Ning ◽  
xiangxin li ◽  
Xiangdong Jian ◽  
Xiaopeng He
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Immune Escape ◽  
Serum Levels ◽  
Control Group ◽  
M2 Macrophages ◽  
Experimental Group ◽  
Group Serum ◽  
Acute Myeloid

Abstract To study the mechanism of Tim-3 on immune escape in benzene-induced acute myeloid leukemia (AML), to provide potential targets of clinical monitoring and intervention of hematological toxicity in benzene-induced AML . C3H/He mice were randomly divided into control group and experimental group. Serum levels of IL-12 in the experimental group were significantly lower than that in the control group. Serum levels of TGF-β1 in the experimental group were significantly higher than that in the control group( p <0.05). The proportion of Tim-3 positive CD14 + monocytes of bone marrow and spleen in the experimental group were both significantly higher than that in the control group ( p <0.05) by Flow cytometry (FCM). Compared with the control group, the expression of Tim-3 on (M1+M2) macrophages of bone marrow in the experimental group significantly increased by immunofluorescence assay. The expression of type M2 macrophages in (M1+M2) macrophages of bone marrow and spleen tissues in the experimental group were both higher than that in the control group. The expression levels of p-PI3K, p-AKT and p-mTOR in the experimental group were all significantly higher than that in the control group. Tim-3 was highly expressed in macrophages in benzene-induced AML. It promoted the activation of PI3K/AKT/mTOR signaling pathway, stimulated the secretion of anti-inflammatory cytokines, and inhibited the secretion of pro-inflammatory cytokines. High expression of Tim-3 changed the phenotype and function of macrophages by promoting the macrophages polarization, thus inducing negative immune response in the tumor microenvironment and tumor immune escape.

Construction of Hyperuricemia Model Rats with Yeast Extract Combined with Oteracil Potassium

2020 ◽  
Author(s):  
Dilidaer Xilifu ◽  
Alimu Kateer ◽  
Nijiati Rehemu ◽  
Zhao-yong Li ◽  
jie Jiang ◽  
...  
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Yeast Extract ◽  
Intraperitoneal Injection ◽  
Rat Kidney ◽  
Optimal Dose ◽  
Serum Levels ◽  
Male Rats ◽  
Control Group ◽  
Optimal Dosage

Abstract Background: Hyperuricemia is the most important risk factor for gout, hypertension, coronary artery disease and other cardiovascular diseases. The incidence of hyperuricemia gradually increased in recent years and it is very necessary to explore the medications of the prevention and treatment of hyperuricemia using hyperuricemia animal models. Objective: The objective of present study is to explore the optimal dose of yeast extract and oteracil potassium in the establishment of hyperuricemia rat model. Method: Sixty-four male rats were randomly divided into 8 experimental groups. Rats were treated with yeast extract by intraperitoneal injection or yeast extract by intraperitoneal injection combined with various doses of oteracil potassium by intragastric feeding or intraperitoneal injection for 28 days. The serum uric acid, urea nitrogen and creatinine levels of different groups were measured at 0th day, 7th day, 14th day, 21th day and 28th day. Results: The serum levels of uric acid in the groups of intraperitoneal injection with yeast extract alone, yeast extract by intraperitoneal injection combined with 50-200 mg/kg oteracil potassium by intragastric feeding and yeast extract by intraperitoneal injection combined with 50-100 mg/kg oteracil potassium by intraperitoneal injection were higher than that in the control group. But we found no significant effect on rat kidney, heart or artery in the above groups. In the group of yeast extract by intraperitoneal injection combined with 200 mg/kg oteracil potassium by intraperitoneal injection, we observed the significantly high level of serum uric acid and morphological and pathological changes in rat kidney, heart and artery. Conclusion: In the present study, we found that continuously treated with yeast extract combined with oteracil potassium is an effective method to establish rat hyperuricemia model. Intraperitoneal injection of yeast extract combined with 200 mg/kg oteracil potassium is an optimal dosage for the construction of a persistent and stable hyperuricemia animal model.

Correlation between Serum and Tissue Levels of Adipokines in Obesity in Adult Male Rats with and without Antioxidant

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
M M Elshawwa
Keyword(s):  
Insulin Resistance ◽  
Adult Male ◽  
Fasting Glucose ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Lipoprotein Cholesterol ◽  
Male Rats ◽  
Control Group ◽  
Tissue Levels ◽  
Group I

Abstract Background Obesity is associated with insulin resistance, type2 diabetes, dyslipidemia and cardiovascular diseases. Apelin and chemerin are identified as adipokines and adipose tissue markers. Several adipose-derived peptides are known to influence food intake, including apelin, whose expression is regulated by insulin and chemerin. Oxidative stress thought to be involved in the development of complications associated with obesity. Objective To study the nature of correlation between serum and liver levels of apelin, chemerin and oxidative parameters in obese rats with and without antioxidant. Aiming to clarify the pathophysiology of obesity. Material and Methods Thirty adult male albino rats, divided into three equal groups. Group I (control), group II (obese) and group III (obese and Lepidium sativum (LS) as an antioxidants). At the end of the experiment, blood samples were collected for estimation of the serum levels of chemerin, apelin, fasting glucose, insulin, insulin resistance (IR), lipid profile, reduced glutathione (GSH) and malondialdehyde (MDA). In addition to tissue homogenous extracts of liver were taken for the levels of MDA, CAT, chemerin and apelin. Results After eight weeks, high fat diet group showed a significant increase in serum levels of apelin, chemerin, fasting glucose, insulin, IR, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) & MDA and a significant decrease in high-density lipoprotein cholesterol (HDL-C) & GSH. HFD also caused a significant increase in tissue levels of MDA, CAT & chemerin and a significant decrease in apelin, compared to control group. While addition of LS to HFD caused a significant decrease in serum levels of apelin, chemerin, fasting glucose, insulin, IR, TC, TG, LDL-C & MDA and a significant increase in HDL-C & GSH. LS also caused a significant decrease in tissue levels of MDA, chemerin & insignificant decrease in CAT and a significant increase in apelin, compared to HFD group. Conclusion This study showed a significant positive correlation between liver & serum chemerin and between liver and serum MDA. On the other hand, it showed a significant negative correlation between liver and serum apelin and liver CAT and serum GSH

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