scholarly journals The Role of Mesenchymal Stem Cells with Ascorbic Acid and N-Acetylcysteine on TNF-α, IL 1β, and NF-κβ Expressions in Acute Pancreatitis in Albino Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Dalia Abdelhafez ◽  
Elshimaa Aboelkomsan ◽  
Abir El Sadik ◽  
Noha Lasheen ◽  
Sara Ashur ◽  
...  

Severe acute pancreatitis (SAP) is a necrotic pancreatic inflammation associated with high mortality rate (up to 70%). Bone marrow (BM) mesenchymal stem cells (MSCs) have been investigated in pancreatic cellular regeneration, but still their effects are controversial. Therefore, the present study is aimed at examining the enrichment of the stem cells with ascorbic acid (AA) and N-acetylcysteine (NAC) and explore their combined action on the expression of the inflammatory cytokines: interleukin 1β (IL 1β), tumor necrosis factor-α (TNF-α), and nuclear factor-κβ (NF-κβ). A total of twenty adult male Sprague-Dawley albino rats were divided into four groups: the control group, cerulein group (to induce acute pancreatitis), BM-MSCs group, and combined BM-MSCs with AA and NAC group. Homing and proliferation of stem cells were revealed by the appearance of PKH26-labelled BM-MSCs in the islets of Langerhans. AA and NAC combination with BM-MSCs (group IV) was demonstrated to affect the expression of the inflammatory cytokines: IL 1β, TNF-α, and NF-κβ. In addition, improvement of the biochemical and histological parameters is represented in increasing body weight, normal blood glucose, and insulin levels and regeneration of the islet cells. Immunohistochemical studies showed an increase in proliferating cell nuclear antigen (PCNA) and decrease in caspase-3 reactions, detected markedly in group IV, after the marked distortion of the classic pancreatic lobular architecture was induced by cerulein. It could be concluded that treatment with BM-MSCs combined with antioxidants could provide a promising therapy for acute pancreatitis and improve the degeneration, apoptosis, necrosis, and inflammatory processes of the islets of Langerhans. TNF-α, IL 1β, and NF-κβ are essential biomarkers for the evaluation of MSC regenerative effectiveness.

2020 ◽  
Vol EJMM29 (4) ◽  
pp. 35-44
Author(s):  
Ahmed H. Bayoumi ◽  
Ahmed El Zainy ◽  
Amul M. Badr ◽  
Dina Fawzy ◽  
Amal A. Elshimy

Background: Doxorubicin is an effective chemotherapeutic drug that commonly induce pathological alteration in skeletal muscles. Bone- marrow mesenchymal stem cells (BMMSCs) offer a therapeutic potential for tissue repair and regeneration. Tumour necrosis factor-alpha (TNF-α) and Interleukin-1 beta (IL-1β) display worthy biomarkers for tissue damage and repair. Objectives: The aim of the current study was to evaluate the therapeutic effect of BMMSCs on doxorubicin - induced skeletal myopathy in experimental animals, through histological studies, antioxidant activity and investigation of TNF-α, IL-1β as diagnostic parameters for muscle damage and regeneration. Methodology: 40 adult albino-rats were divided into 4 equal groups; Group-I (control group) injected with phosphate-buffered saline (PBS), Group-II: doxorubicin- induced myopathy model group; received no treatment, Group-III: doxorubicin- induced myopathy model left for spontaneous muscle recovery, and Group-IV: doxorubicin- induced myopathy treated with systemic BMMSCs. The skeletal muscle regeneration evaluated through histological and antioxidant activity studies and investigation of TNF-α, IL-1β and vascular endothelial growth factor (VEGF) levels. Results: Photomicrographic studies of the muscle fibers showed a more evident regeneration in MSCs treated groups (IV) when compared with the other groups received no treatment. A significant reduced levels of TNF-α, IL-1β, and increased both VEGF and antioxidant activity were demonstrated in group IV when compared with the other groups received no treatment. Conclusion: MSCs is a promising therapy for doxorubicin-induced skeletal myopathy. TNF-α, and IL-1β are helpful biomarkers for evaluation of SCs therapeutic efficacy.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shengchao Zhang ◽  
Jiankai Fang ◽  
Zhanhong Liu ◽  
Pengbo Hou ◽  
Lijuan Cao ◽  
...  

Abstract Background Muscle stem cells (MuSCs) are absolutely required for the formation, repair, and regeneration of skeletal muscle tissue. Increasing evidence demonstrated that tissue stem cells, especially mesenchymal stem cells (MSCs), can exert therapeutic effects on various degenerative and inflammatory disorders based on their immunoregulatory properties. Human mesenchymal stem cells (hMSCs) treated with interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were reported to possess anti-inflammatory functions by producing TNF-stimulated gene 6 (TSG-6). However, whether human muscle stem cells (hMuSCs) also possess TSG-6 mediated anti-inflammatory functions has not been explored. Methods The ulcerative colitis mouse model was established by subjecting mice to dextran sulfate sodium (DSS) in drinking water for 7 days. hMuSCs were pretreated with IFN-γ and TNF-α for 48 h and were then transplanted intravenously at day 2 of DSS administration. Body weights were monitored daily. Indoleamine 2,3-dioxygenase (IDO) and TSG-6 in hMuSCs were knocked down with short hairpin RNA (shRNA) and small interfering RNA (siRNA), respectively. Colon tissues were collected for length measurement and histopathological examination. The serum level of IL-6 in mice was measured by enzyme-linked immunosorbent assay (ELISA). Real-time PCR and Western blot analysis were performed to evaluate gene expression. Results hMuSCs treated with inflammatory factors significantly ameliorated inflammatory bowel disease (IBD) symptoms. IDO and TSG-6 were greatly upregulated and required for the beneficial effects of hMuSCs on IBD. Mechanistically, the tryptophan metabolites, kynurenine (KYN) or kynurenic acid (KYNA) produced by IDO, augmented the expression of TSG-6 through activating their common receptor aryl hydrocarbon receptor (AHR). Conclusion Inflammatory cytokines-treated hMuSCs can alleviate DSS-induced colitis through IDO-mediated TSG-6 production.


2021 ◽  
Vol 11 (9) ◽  
pp. 1838-1843
Author(s):  
Xiaohong Zhou ◽  
Xuzhong Hao ◽  
Feifei He

To investigate whether exosomes (exo) derived from human umbilical cord mesenchymal stem cells (huMSCs) and microRNA (miRNA)-342 have a protective effect on severe acute pancreatitis (SAP). Human umbilical cord blood was collected to extract huMSC-exo. With sham-operated mice as control group (n = 10), the other mice were induced to SAP model (n = 20), while 10 of the SAP mice received treatment with huMSC-exo. ELISA was performed to determine amylase and TAP level as well as inflammatory factors and HE staining to evaluate pathological changes of pancreatic tissue. The expression of miR-342 and Shh, Ptchl, and Smo in the Hh signal pathway was detected using RT-qPCR. The expression of miR-342 and the mRNA expression of Shh, Ptchl, and Smo was higher than that in model group (p < 0.05). The level of serum amylase, trypsinogen, and IFN-γ,Fasl, and IL-6 was upregulated in pancreas tissues of SAP mice relative to healthy mice, but their levels were decreased upon treatment with huMSC-exo and slightly higher than those of the control group, just not significantly. Collectively, the huMSC-exo may activate the Hh signaling pathway by regulating the expression of miR-342 increasing the expression of Shh, Ptchl, and Smo, and thereby healing of damaged pancreatic tissues in SAP.


2022 ◽  
Vol 12 (5) ◽  
pp. 1034-1039
Author(s):  
Xiaoxiang Wang ◽  
Lan Yu ◽  
Xing Xiong ◽  
Yao Chen ◽  
Bo Men

Bone marrow mesenchymal stem cells (BMSCs) are capable of multipolar differentiation and repairing injured tissues. Herein, we aimed to investigate the mechanism by how BMSCs modulate the apoptotic pathway in the acute pancreatitis (AP). In this study, primary BMSCs were cultured and administrated into 10 AP mice while 10 healthy mice were taken as a blank group and 10 AP mice as a control group. The mouse pancreatic tissues were assessed by HE staining and evaluated by pancreatitis score and serum amylase detection. Level of inflammatory factors CRP and TNF-α was measured by ELISA and PIPK1, PIPK3, MLKL and Caspase-8 expression was detected by RT-qPCR and Western blot. The pancreatitis score (7.29±1.36) and the serum amylase score of (453.66±103.67) mu/ml of BMSCs group was significantly higher than that of control group, indicating increased tissue repair after BMSCs treatment. BMSCs group exhibited a higher level of CRP (711.01±115.31) and TNF-α (132.81±22.13) in serum compared to control group (p < 0.05). PIPK1, PIPK3, and MLKL expression in BMSCs group decreased (p < 0.05) whereas Caspase-8 was increased (p < 0.05). On the other hand, BMSCs group presented upregulated PIPK1, PIPK3, and MLKL (p < 0.05) and downregulated Caspase-8 (p < 0.05). In conclusion, BMSCs regulate cell apoptosis by upregulating Caspase-8 expression, and downregulating PIPK1, PIPK3 and MLKL level, thereby alleviating the inflammation in AP.


2019 ◽  
Vol 8 (12) ◽  
pp. 2211 ◽  
Author(s):  
Christian Behm ◽  
Alice Blufstein ◽  
Johannes Gahn ◽  
Barbara Kubin ◽  
Michael Nemec ◽  
...  

Periodontal ligament-derived mesenchymal stem cells (hPDLSCs) possess immunomodulatory abilities which are strongly enhanced by various inflammatory cytokines. Vitamin D3 has anti-inflammatory effects on hPDLSCs and immune cells. However, no study to date has directly compared the influence of 1,25(OH)2D3 on the immunomodulatory activities of hPDLSCs in the presence of different cytokines. In the present study, the effects of hPDLSCs treated with tumor necrosis factor (TNF)-α, interleukin (IL)-1β, or interferon (IFN)-γ in the presence of 1,25(OH)2D3 on the proliferation of allogenic CD4+ T lymphocyte or on the functional status of primary CD68+ macrophages were analyzed in coculture models. Additionally, the effects of 1,25(OH)2D3 on TNF-α-, IL-1β-, and IFN-γ-induced gene expression of some immunomodulatory factors in hPDLSCs were compared. Under coculture conditions, 1,25(OH)2D3 increased or decreased CD4+ T lymphocyte proliferation via hPDLSCs, depending on the cytokine. hPDLSCs primed with 1,25(OH)2D3 and different cytokines affected pro- and anti-inflammatory cytokine expression in macrophages variably, depending on the priming cytokine. With one exception, 1,25(OH)2D3 significantly reduced TNF-α-, IL-1β-, and IFN-γ-induced expression of all the investigated immunomediators in hPDLSCs, albeit to different extents. These results suggest that 1,25(OH)2D3 influences the immunomodulatory activities of hPDLSCs depending qualitatively and quantitatively on the presence of certain inflammatory cytokines.


Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 4870
Author(s):  
Abdelsamed I. Elshamy ◽  
Naglaa M. Ammar ◽  
Heba A. Hassan ◽  
Walaa A. El-Kashak ◽  
Salim S. Al-Rejaie ◽  
...  

Wounds and burn injury are major causes of death and disability worldwide. Myricetin is a common bioactive flavonoid isolated naturally from the plant kingdom. Herein, a topical application of naturally isolated myricetin from the shoots of Tecomaria capensis v. aurea on excisional wound healing that was performed in albino rats. The wounded rats were treated every day with 10 and 20% myricetin for 14 days. During the experiment, the wound closure percentage was estimated at days 0, 7, and 14. Effects of myricetin on the inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and cluster of differentiation 68 (CD68) in the serum were evaluated using immunosorbent assay kits. The percentage of wound closure and contraction was delayed in wounded rats (67.35%) and was remarkably increased after treatment of wounded rats with myricetin; the treatment with 20% myricetin was the most potent (98.76%). Histological findings exhibited that 10% myricetin caused the formation of a large area of scarring at the wound enclosure and stratified squamous epithelium without the formation of papillae as in the control group. Treatment with 20% myricetin exhibited less area of scarring at the wound enclosure as well as re-epithelialization with a high density of fibroblasts and blood capillaries in the wound. Level elevations of serum pro-inflammatory cytokines, IL-1β, and TNF-α and macrophage CD68 were decreased in wounded rats treated with myricetin. Thus, it can be suggested that the enhancements in inflammatory cytokines as well as systemic reorganization after myricetin treatment may be recommended to play a crucial part in the promotion of wound healing. The findings suggest that treatment with a higher dose of myricetin was better in improving wound curing in rats. It could serve as a potent anti-inflammatory agent and can be used as an adjunctive or alternative agent in the future.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Hang Zhao ◽  
Zhiying He ◽  
Dandan Huang ◽  
Jun Gao ◽  
Yanfang Gong ◽  
...  

Background & Aims. Severe acute pancreatitis (SAP) remains a high-mortality disease. Bone marrow (BM) mesenchymal stem cells (MSCs) have been demonstrated to have plasticity of transdifferentiation and to have immunomodulatory functions. In the present study, we assessed the roles of MSCs in SAP and the therapeutic effects of MSC on SAP after transplantation.Methods. A pancreatitis rat model was induced by the injection of taurocholic acid (TCA) into the pancreatic duct. After isolation and characterization of MSC from BM, MSC transplantation was conducted 24 hrs after SAP induction by tail vein injection. The survival rate was observed and MSCs were traced after transplantation. The expression of TNF-αand IL-1βmRNA in the transplantation group was also analyzed.Results. The survival rate of the transplantation group was significantly higher compared to the control group (p<0.05). Infused MSCs were detected in the pancreas and BM 3 days after transplantation. The expression of TNF-αand IL-1βmRNA in the transplantation group was significantly lower than in the control group in both the pancreas and the lungs (p<0.05).Conclusions. MSC transplantation could improve the prognosis of SAP rats. Engrafted MSCs have the capacity of homing, migration, and planting during the treatment of SAP.


2021 ◽  
Vol 9 (A) ◽  
pp. 798-801
Author(s):  
Muhammad Oky Prabudi ◽  
M. F. G. Siregar ◽  
I. P. A. Nasution ◽  
S. Ilyas

BACKGROUND: Endometritis is a gynecological disease characterized by inflammation of the endometrial glands and stroma. Inflammatory stimuli or tissue injury induce inflammatory pain through the release of cytokines. Ascorbic acid (AA) is a water-soluble Vitamin that plays a role in inhibiting the production of proinflammatory cytokines and increases the expression of anti-inflammatory cytokines. AIM: The purpose of this study was to find out the association between administration of AA and inflammatory cytokines in experimental animals Rattus norvegicus with endometritis. METHODS: The research was conducted using virgin female R. norvegicus laboratory mice weighing 250–300 g and aged 11–12 weeks with an estrus cycle of 5–6 days. Mice with regular oestrous cycles were randomly divided into three groups: group 1 was given 200 L of water orally without Escherichia coli inoculation and represented a negative control. Groups 2 and 3 were inoculated (50 L/rat) E. coli intravaginally, 106 colony-forming unit/mL, Group 2 was not given AA and the other side Group 3 was assigned AA. The interleukin (IL)-10 and tumor necrosis factor (TNF)-α _cytokines examination was carried out by histopathological examination through a biopsy of the endometrial tissue. Hypothesis testing on the data was analyzed by the Kruskal Wallis test using Statistical Package for Social Sciences. RESULTS: Data from the current study revealed that the highest mean value of IL-10 was found in the negative control group (2.5) and the lowest value in the positive control group (1.3). Regarding TNF-α _the highest mean value (2.8) was found in the treatment group and the lowest mean value (2.1) was found in the treatment group. Using the Kruskal Wallis test, IL-10 and TNF-α _showed insignificant results (p = value 0.304 and 0.145 respectively). CONCLUSIONS: The administration of AA did not affect the decrease in TNF-α _or the upregulation of IL-10 as anti-inflammatory cytokines.


2017 ◽  
Vol 4 (02) ◽  
pp. 1128
Author(s):  
Nadia H. Ismaeil ◽  
Amany A. Osman ◽  
Elham H.A. Ali ◽  
Laila A. Rashed ◽  
Manal A. Saleh

Introduction: The present work aims to examine the possible role of stem cells on biochemical markers and histopathological alterations of hypoxia caused by sodium nitrite (NaNO2) toxicity in testes of male rats. Methods: In this study, 96 adult male albino rats were divided into 6 groups (16 rats each). Group 1 (G1) was the control group and received distilled H2O. Group 2 (G2) received daily NaNO2 (35 m/kg bwt/ day) via subcutaneous injection for 3 weeks. Group 3 (G3) received NaNO2 for 2 weeks and were then injected once with 2*106 mesenchymal stem cells (MSCs) intravenously and sacrificed 4 weeks later. Group 4 (G4) received NaNO2 for 2 weeks and were then injected with 2*106 MSCs followed by daily NaNO2 injection for 1 week; rats in G4 were sacrificed 4 weeks from MSCs treatment. Group 5 (G5) rats were treated with NaNO2 for 2 weeks and then left to recover for 4 weeks. Finally, Group 6 (G6) rats were treated with NaNO2 for 3 weeks and left to recover for 3 weeks, after which point they were sacrificed. Results: The results showed that NaNO2 caused oxidative damage and histopathological alterations in the rat testes, as well as increased the levels of testes malondialdehyde (MDA), nitric oxide (NO) and DNA fragmentation percentage (DNA F %). Moreover, NaNO2 decreased the elevated activities of testes catalase (CAT) and total antioxidant activity (TAA), in comparison to the control group. The histological results illustrated different distortions, vacuolization and lipid accumulations in interlobular space as well as diminution of inter cellular germ cell layers, absence of Leydig cells, irregular basement membrane of tubule, and separation within spermatogenic cells. In addition, congestion and dilation of intertubular and peripheral blood capillaries were found. Nevertheless, the administration of stem cells reduced the danger actions of sodium nitrite by enhancing biochemical marker concentration. Conclusion: There was an improvement in the histology of the rat testes, including a relatively normal order in the different stages of spermatogonia and loss of different stages of spermatocytes. Regarding the recovery period, there was also a significant improvement in each of the biochemical parameters assessed and in the histological lesions.


2021 ◽  
Vol 11 (22) ◽  
pp. 10900
Author(s):  
Abdulsamet Emet ◽  
Erdi Ozdemir ◽  
Duygu Uckan Cetinkaya ◽  
Emine Kilic ◽  
Ramin Hashemihesar ◽  
...  

The high costs and extensive time needed for the treatment of critical-sized bone defects are still major clinical concerns in orthopedic surgery; therefore, researchers continue to look for more cost and time-effective methods. This study aims to investigate the effects of a decellularized omentum scaffold with a combination of platelet-rich plasma (PRP) and mesenchymal stem cells on the healing of critical-sized bone defects. Wistar albino rats (n = 30) were investigated in five groups. Critical-sized bone defects were formed on bilateral radius shafts. No scaffold, decellularized omentum, omentum with PRP and omentum + mesenchymal stem cells was used in group 1 (control group), 2, 3 and 4, respectively. In addition, omentum with a combination of mesenchymal stem cells +PRP was used in group 5. After 6 weeks, both radiological and histological healing were evaluated comparatively among the groups. After the use of a decellularized omentum scaffold, vitality of new cells was maintained, and new bone formation occurred. When compared to the control group, radiological healing was significantly better (p = 0.047) in the omentum and omentum + PRP-treated groups. Furthermore, histological healing was better in the omentum and omentum + PRP-treated groups than the control group (p = 0.001). The use of a decellularized omentum scaffold is suitable in the healing of critical bone defects.


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