scholarly journals Silencing microRNA155 transforms the properties of endotoxin tolerant dendritic cells and enhance its therapeutic effect on sepsis murine model.

2020 ◽  
Author(s):  
Min Yang ◽  
Chao-Chen Hou ◽  
Yan-Yan Yang ◽  
Shan-Shan Li ◽  
De-Yong Kong ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Treatment Group ◽  
Murine Model ◽  
Critical Role ◽  
Endotoxin Tolerance ◽  
Sepsis Group ◽  
Control Group ◽  
Sham Operation ◽  
Therapeutic Effects ◽  
Sham Operation Group

Abstract Sepsis refers to the body's dysfunctional response to infection and leads to life-threatening organ dysfunction. Dentritic cells (DCs), a kind of powerful functional antigen-presenting cell, plays a critical role in immune response and has been used in the field of immunotherapy for multiple diseases. Endotoxin tolerance is a phenomenon that believed to prevent the organism from producing persistent and excessive inflammatory reaction and numerous studies indicated that endotoxin tolerant dendritic cells (ETDCs) have therapeutic effects on experimental models of several diseases. MicroRNA155(miR155), which plays a pivotal role in various physiological and pathological processes in immunity, was reported associated with the formation of endotoxin tolerance. In this paper, we explored the change of properties after silencing miR155 in ETDCs then attempted to study its effects on the murine model of sepsis. Endotoxin tolerant dendritic cells were transfected with adenovirus silencing miR155 and negative control adenovirus, thereafter collected for reverse transcription polymerase chain reaction of miR155, costimulatory molecules analysis, allogeneic mixed lymphocyte reaction and cytokine concentration evaluation. 42 balb/c mice were randomly divided into control group, sham operation group, sepsis group, ETDCs treatment group and miR155-/-ETDCs treatment group. Two treatment groups respectively received tail vein injection of ETDCs and miR155-/-ETDCs 24h earlier than cacal ligation puncture. Our results revealed that silencing miR155 could deepen the immature status of ETDCs and both ETDCs and miR155-/-ETDCs performed a protective effect in murine sepsis models while miR155-/-ETDCs got a better protection. We reasoned that miR155 participates the formation of endotoxin tolerance and the protective effects of ETDCs and miR155-/-ETDCs in the early stage of sepsis may achieved by altering the concentration of mouse cytokines to affect T cell differentiation and exert negative immune regulation.

A long-term survival rat model of spinal cord ischemia injury: Thoracic aortic occlusion combined with aortic bypass circulation

Vascular ◽  
2021 ◽  
pp. 170853812110601
Author(s):  
Cheng-yong Yin ◽  
Jun-jie Fei ◽  
Yu-yin Duan ◽  
Ke Yang ◽  
Xin Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Treatment Group ◽  
Thoracic Aorta ◽  
Aortic Occlusion ◽  
Control Group ◽  
Sham Operation ◽  
Term Survival ◽  
Sham Operation Group ◽  
Aortic Bypass ◽  
Operation Group

Objective This study aims to investigate the methods for rat spinal cord ischemia injury models with a high long-term survival rate. Methods The rats were divided into three groups: the treatment group, the control group, and the sham operation group. The treatment group had a blocked thoracic aorta (landing zone 3 by Ishimaru – T11) + aortic bypass circulation for 20 min. In the control group, the thoracic aorta at the landing zone 3 was blocked for 20 min. In the sham operation group, only thoracotomy without thoracic aortic occlusion was performed. The mean arterial blood pressure (MABP) of the thoracic aorta and caudal artery before and after thoracic aortic occlusion was monitored intraoperatively. Spinal cord function was monitored by a transcranial motor evoked potential (Tc-MEP) during the operation. Spinal cord function was evaluated by the BBB scale (Basso, Beattie, & Bresnahan locomotor rating scale) scores at multiple postoperative time points. The spinal cord sections of the rats were observed for 7 days after surgery, and the survival curves were analyzed for 28 days after surgery. Results After aortic occlusion, the MABP of thoracic aorta decreased to 6% of that before occlusion, and the MABP of caudal artery decreased to 63% of that before occlusion in the treatment group. In the control group, the MABP of both thoracic aorta and caudal artery decreased to 19% of that before occlusion. The Tc-MEP waveform of the treatment group disappeared after 6 min, and that of the control group disappeared after 8 min until the end of surgery. There was no change in the Tc-MEP waveform in the sham operation group. The BBB score of the treatment group decreased more obviously than the control group, and there was a significant difference. There was no decrease in the sham group. Spinal cord sections showed a large number of degeneration and necrosis of neurons, infiltration of inflammatory cells, and proliferation of surrounding glial cells in the treatment group. In the control group, multiple neurons were necrotic. The histology of the sham operation group was normal. The 28-day survival rate of the treatment group was 73.3%, which was higher than the control group (40.0%), and there was a significant difference ( p < 0.05). Conclusion Thoracic aortic occlusion combined with aortic bypass is an effective modeling method for rats with accurate modeling effects and high long-term survival rates.

scholarly journals Comparative study on the antituberculous effect and mechanism of the traditional Chinese medicines NiuBeiXiaoHe extract and JieHeWan

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Li-Yao Duan ◽  
Yan Liang ◽  
Wen-Ping Gong ◽  
Yong Xue ◽  
Jie Mi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chinese Medicine ◽  
Treatment Group ◽  
Mechanism Of Action ◽  
Cell Damage ◽  
Control Group ◽  
Therapeutic Effects ◽  
Model Group ◽  
Lung Histopathology ◽  
Th17 Cytokines

Abstract Background The traditional Chinese medicine NiuBeiXiaoHe (NBXH) extract and Chinese medicine preparation JieHeWan (JHW) exhibit anti-tuberculosis effects. The anti- tuberculosis effect of NBXH was compared with that of JHW to elucidate the mechanism of action of NBXH. Methods BALB/c mice aged 6-8 weeks were randomly divided into a normal control group, Tuberculosis (TB) model group, JHW treatment group, and NBXH treatment group. After 3 and 13 weeks of treatment, the therapeutic effect in each group was evaluated by comparing lung histopathology, lung and liver colony counts, the number of spots representing effector T cells secreting IFN-γ in an ELISPOT, and the levels of Th1, Th2, and Th17 cytokines, which were measured by a cytometric bead array (CBA). Mouse RNA samples were subjected to transcriptome sequencing. Results After 13 weeks of treatment, the mean histopathological lesion area of the NBXH group was significantly smaller than that of the TB model group (P < 0.05). Compared with those in the TB model group, the lung colony counts in the JHW and NBXH groups were significantly decreased (P < 0.05), and the IL-2 and IL-4 levels in the NBXH group were significantly increased (P < 0.05). NBXH partly restored significant changes in gene expression caused by Mycobacterium tuberculosis (M. tuberculosis) infection. According to GO and KEGG analyses, the changes in biological process (BP), cell composition (CC) and molecular function (MF) terms and in signaling pathways caused by NBXH and JHW treatment were not completely consistent, but they were mainly related to the immune response and inflammatory response in the mouse TB model. Conclusions NBXH had therapeutic effects similar to those of JHW in improving lung histopathology, reducing lung colony counts, and regulating the levels of cytokines. NBXH restored significant changes in gene expression and repaired cell damage caused by M. tuberculosis infection by regulating immune-related pathways, which clarified the mechanism of action of NBXH.

scholarly journals Murine hepatoma treatment with mature dendritic cells stimulated by Trichinella spiralis excretory/secretory products

Parasite ◽  
2020 ◽  
Vol 27 ◽  
pp. 47
Author(s):  
Jing Ding ◽  
Xiaolei Liu ◽  
Bin Tang ◽  
Xue Bai ◽  
Yang Wang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Growth ◽  
Antitumor Effect ◽  
Trichinella Spiralis ◽  
Critical Role ◽  
Tumor Model ◽  
Control Group ◽  
Tumor Inhibition ◽  
Significant Difference ◽  
Secretory Products

Excretory/Secretory Products (ESPs) of the nematode Trichinella spiralis contain antitumor-active substances that inhibit tumor growth. Mature dendritic cells (DCs) play a critical role in the antitumor immunity of the organism. As pathogen-derived products, it ought to be discussed whether T. spiralis ESPs will reduce the antitumor effect of mature DCs from the host before it is applied to patients’ tumors. Therefore, the aim of this work was to evaluate the immunological effect of DCs stimulated by T. spiralis ESPs in H22 tumor-bearing mice. H22 tumor model mice in this study were randomly divided into four groups according to the treatment: PBS control group, ESP group, DCs group, and DCs stimulated with T. spiralis ESP (ESP+DCs group). The antitumor effect was evaluated by tumor inhibition rate and cytokine detection using ELISA. The results showed significant inhibition in tumor growth in the ESP+DCs, DCs and ESP groups when compared with the PBS control group (p < 0.01, p < 0.01, and p < 0.05, respectively). However, no significant difference was observed on tumor inhibition rates between the ESP+DCs and DCs groups. The decrease in IL-4, IL-6, and IL-10, and the increase in IFN-γ between the DCs and ESP+DCs groups were also not significant. Therefore, DCs stimulated by ESP did not reduce the antitumor effect of mature DCs, which demonstrated that the T. spiralis ESP would not affect the antitumor effect of mature DCs by modulating the immune response of the host, and that ESPs are safe in antitumor immunology when applied in a tumor model mice.

Abstract 13287: Dendritic Cells Play a Critical Role in the Initiation of Atherosclerosis

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Mengyao Jin ◽  
Peng Liu
Keyword(s):  
Cell Proliferation ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Critical Role ◽  
Cell Interaction ◽  
Plaque Formation ◽  
T Cell Proliferation ◽  
Control Group

Introduction: Dendritic cells (DCs) that are known as professional antigen-presenting cells have been found to pre-locate in non-inflammatory arterial wall and increasingly accumulate during atherosclerosis progression. Previous findings suggested that residential DCs in the intima are responsible for capturing modified lipids and forming foam cells during the initiation of atherosclerosis. Hypothesis: DC accumulation and enhanced DC-T cell interaction play a critical role in the initiation of atherosclerosis. Methods: We measured plaque formation, vascular DC accumulation and antigen-specific T cell proliferation mediated by isolated aortic cells in ApoE-/- mice, as well as DTR-CD11c/ApoE-/- or DTR-CD11b/ApoE-/- mice for conditional depletion of DCs or macrophages, respectively. A brief high-fat diet for 10 days was used as a model of initial atherosclerosis. Results: In addition to increased intimal DC accumulation and plaque formation in aortic roots, 10 days of HFD induced T cell infiltration in ApoE-/- mice, compared to those without HFD as the control. Isolated aortic cells from mice with 10-day HFD showed stronger capability in inducing antigen-specific T cell proliferation, compare to the control (HFD: 3.14±0.71%; no HFD: 1.56±0.36%; p=0.022). Single diphtheria toxin (DT) injection at day 1 yielded approximately 50% decrease in intimal DC accumulation, as well as 60% attenuation in plaque formation in DTR-CD11c/ApoE-/- mice after 10-day HFD. Capability of stimulating antigen-specific T cell proliferation was also impaired in aortic cells from DC-depleted mice (DT-treated: 1.62±0.30%; PBS-treated: 3.04±0.59%; p= 0.004), along with reduction in indirect conduction of T cell activation. In contrast, no significant changes were found in plaque formation and DC accumulation in DT-injected DTR-CD11b/ApoE-/- mice after 10 days of HFD, compared to control group. Furthermore, depletion of CD11b+ macrophages in either aortas or spleens didn’t alter capability of inducing antigen-specific T cell proliferation in DT-injected mice. Conclusions: These results suggested that vascular DCs rather than macrophages play a more important role in T cell activation and initiation of atherosclerosis.

scholarly journals The Effects of Chinese Medicine QRD, Antibiotics, and Probiotics on Therapy and Gut Microbiota in Septic Rats

2021 ◽  
Vol 11 ◽  
Author(s):  
Huiling Cao ◽  
Chunhui Zong ◽  
Wenkui Dai ◽  
Qiaoying Gao ◽  
Donghua Li ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Gut Microbiota ◽  
Survival Rates ◽  
Amplicon Sequencing ◽  
Medical Emergency ◽  
Control Group ◽  
Rrna Gene ◽  
Sham Operation ◽  
Therapeutic Effects

Sepsis is a common and often treacherous medical emergency with a high mortality and long-term complications in survivors. Though antibiotic therapy can reduce death rate of sepsis significantly, it impairs gut microbiota (GM), which play imperative roles in human health. In this study, we compared the therapeutic effects of antibiotics, probiotics, and Chinese medicine QRD on the survival rates of septic model and observed the GM characteristics of experimental rats via 16S rRNA gene amplicon sequencing. The 72 h survival rates of septic rat demonstrated the significant therapeutic effects in the three groups treated with antibiotics (AT), Chinses medicine QRD (QT), and probiotics (PT), which were elevated from the survival rate of 26.67% for the sepsis control group (ST) to 100.0% for AT, 88.24% for QT, and 58.33% for PT. The original characteristics of GM identified in the sham operation controls (SC) were relatively similar to those in PT and QT; nevertheless, the AT rats were shown dramatically decreased in the GM diversity. In addition, the septic rats in AT were revealed the higher abundances of Escherichia Shigella, Proteus, Morganella, Enterococcus, and Lysinibacillus, but the lower those of Parabacteroides, Alistipes, Desulfovibrio, Bacteroides, Helicobacter, Mucispirillum, Oscillibacter, Lachnospiraceae, and Ruminiclostridium 9, when compared to the PT and QT rats. By contrast, the GM of PT and QT rats shared similar diversity and structure. Our findings indicated that QRD increased the survival rates without impairment of the GM characteristics, which provides novel insights into the role of Chinese medicine in therapy and long-term recovery of sepsis.

scholarly journals Clinical Study of Acupotomy Trinity Lysis on Cervical Spondylotic Myelopathy with Liver and Kidney Deficiency Syndrome

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Jianyong Gao ◽  
Yi Zhao ◽  
Tinglan Sun ◽  
Weike Liu ◽  
Zhenguo Wang
Keyword(s):  
Treatment Group ◽  
Cervical Spondylotic Myelopathy ◽  
Deficiency Syndrome ◽  
Control Group ◽  
Therapeutic Effects ◽  
Kidney Deficiency ◽  
Significant Difference ◽  
Before And After ◽  
Liver And Kidney ◽  
Experimental Group

Objective: To compare the therapeutic effects of acupotomy trinity lysis and traditional acupotomy on cervical spondylotic myelopathy. Methods: A total of 205 patients with cervical spondylotic myelopathy of liver and kidney deficiency syndrome were randomly divided into the experimental group (105 cases) and the control group (100 cases). The experimental group was relaxed with acupotomy in three positions: Heaven (tian), Human (ren) and Earth (di). Traditional acupotomy was used to relax Ashi acupoints of the affected vertebra in the control group. One treatment was conducted in one week, and the duration of one course of treatment was three weeks. The VAS, JOA score and NDI index were observed after treatment.  Results: Before and after treatment, the total treatment efficiency of the treatment group was 95.23%, and that of the control group was 80.00%, there was significant difference between the two groups, P<0.05; Before operation, there was no significant difference in JOA score, NDI index score, and VAS score between the treatment group and the control group (P>0.05); there was no significant difference after 1 week (P>0.05), but there were significant differences between the two groups 2 weeks and 3 weeks after operation (P<0.05). Conclusion: Acupotomy trinity lysis is a safe, effective and economical treatment for cervical spondylotic myelopathy.

The Efficacy and Mechanism of Autologous Fat Stem Cells Combined with Microcarrier 6 Transplantation for Anal Fistula Treatment

2020 ◽  
Author(s):  
Yansen Li ◽  
Mingfeng Fan ◽  
Hanxiang Le ◽  
Xiangjun Xu ◽  
Shuai Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Treatment Group ◽  
Anal Fistula ◽  
Striated Muscle ◽  
Muscle Cells ◽  
Rubber Band ◽  
Control Group ◽  
Therapeutic Effects ◽  
Fistula Healing ◽  
Operation Group

Abstract Background: Adipose-derived stem cells (ASCs) function in multi-directional differentiation, proliferation, and tissue regeneration. It is not clear whether microcarrier 6 can promote the migration, differentiation, and regeneration of fat stem cells, and improve therapeutic effects for the treatment of anal fistula.Methods: Japanese big ear rabbits were employed to establish an anal fistula model, and ASC-microcarrier 6 mixed transplantation was used as a treatment. HE staining, immunohistochemistry, and RNA sequencing were used to observe the effect of ASC-microcarrier 6 transplantation on anal fistula healing, in comparison with the ASC treatment group, rubber band operation group, and control group.Results: HE staining indicated scattered striated muscle cells and epithelial tissues in fistula tissues of the ASC-microcarrier 6 complex group and the ASC treatment group, while a small number of lymphocytes were clustered around the microcarrier 6, and fat cell aggregation was seen in the ASC treatment group. RNA sequence analysis showed that differential genes were mainly concentrated in striated muscle cells, vascular smooth muscle, and other tissues. PI3K/AKT signaling pathway molecules were significantly enriched, granulation tissue and lymphocyte infiltration were observed in the rubber band string operation group, and a large amount of necrotic tissue was seen in the control group.Conclusion: Microcarrier 6 is beneficial to the multi-directional differentiation of ASCs, which can provide a good environment for the survival of ASCs and promote fistula healing.

Efficacy of electroacupuncture plus warm needling therapy for plantar heel pain: a randomised waitlist-controlled trial

2020 ◽  
pp. 096452842094604
Author(s):  
Lai Fun Ho ◽  
Yuanqi Guo ◽  
Jessica Yuet-Ling Ching ◽  
Kam Leung Chan ◽  
Ping Him Tsang ◽  
...  
Keyword(s):  
Treatment Group ◽  
Controlled Trial ◽  
Heel Pain ◽  
Community Dwelling ◽  
Control Group ◽  
Therapeutic Effects ◽  
Global Rating ◽  
Plantar Heel Pain ◽  
Foot Function ◽  
Warm Needling

Objective: To investigate the therapeutic effects of electroacupuncture plus warm needling (EAWN) therapy on pain and foot function in adults with plantar heel pain (PHP). Methods: This prospective, randomised, parallel-group, waitlist-controlled trial was conducted at a Chinese medicine centre in Hong Kong between May 2018 and February 2019. Eighty eligible community-dwelling subjects with PHP (mean age 59.7 years; 85% female) were equally randomised to receive EAWN therapy or remain on a waitlist. The treatment group received six 30-min sessions of standardised EAWN therapy over 4 weeks; the control group received no treatment. The outcome measures were the visual analogue scale (VAS) score for first-step pain, foot function index (FFI) scores and global rating of change (GRC) scale scores. Assessments were made at baseline, week 2 and week 4 (primary endpoint). The treatment group underwent additional assessments at week 8. Outcomes were evaluated by intention-to-treat analysis. Results: Patients who received EAWN therapy exhibited greater improvements in the mean first-step pain VAS and all FFI scores than did those in the control group at weeks 2 and 4, with significant between-group differences (all P < 0.001). Compared with baseline, there were significant decreases in mean first-step pain VAS scores at weeks 2 and 4, and FFI scores at week 4, in the treatment group but not in the control group. The improvements in the treatment group continued until week 8. GRC scores at week 4 indicated improvement in all treated patients and only 22.5% of the control group patients ( P < 0.001). There were no study-related adverse events. Conclusion: EAWN therapy could be an effective treatment for PHP in middle-aged and older adults. Trial registration number: ChiCTR1800014906 (Chinese Clinical Trials Registry)

scholarly journals Synergistic Effects of Mesenchymal Stem Cell Transplantation and Repetitive Transcranial Magnetic Stimulation on Promoting Autophagy and Synaptic Plasticity in Vascular Dementia

2018 ◽  
Vol 74 (9) ◽  
pp. 1341-1350 ◽  
Author(s):  
Fei Wang ◽  
Chi Zhang ◽  
Siyuan Hou ◽  
Xin Geng
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Vascular Dementia ◽  
Magnetic Stimulation ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Synergistic Effects ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Sham Operation ◽  
Therapeutic Effects ◽  
Mesenchymal Stem Cell Transplantation

Abstract Repetitive transcranial magnetic stimulation (rTMS) and mesenchymal stem cells (MSCs) transplantation both showed therapeutic effects on cognition impairment in vascular dementia (VD) model rats. However, whether these two therapies have synergistic effects and the molecular mechanisms remain unclear. In our present study, rats were randomly divided into six groups: control group, sham operation group, VD group, MSC group, rTMS group, and MSC+rTMS group. The VD model rats were prepared using a modified 2VO method. rTMS treatment was implemented at a frequency of 5 Hz, the stimulation intensity for 0.5 Tesla, 20 strings every day with 10 pulses per string and six treatment courses. The results of the Morris water maze test showed that the learning and memory abilities of the MSC group, rTMS group, and MSC+rTMS group were better than that of the VD group, and the MSC+rTMS group showed the most significant effect. The protein expression levels of brain-derived neurotrophic factor, NR1, LC3-II, and Beclin-1 were the highest and p62 protein was the lowest in the MSC+rTMS group. Our findings demonstrated that rTMS could further enhance the effect of MSC transplantation on VD rats and provided an important basis for the combined application of MSC transplantation and rTMS to treat VD or other neurological diseases.

scholarly journals Experimental study of the effects of hypoxia simulator on osteointegration of titanium prosthesis in osteoporotic rats

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jiangfeng Liu ◽  
Huijun Kang ◽  
Jiangfeng Lu ◽  
Yike Dai ◽  
Fei Wang
Keyword(s):  
Signaling Pathway ◽  
Control Group ◽  
Osteoporotic Bone ◽  
Sham Operation ◽  
Mrna Levels ◽  
Micro Ct ◽  
Sprague Dawley ◽  
Micro Computed Tomography ◽  
Sham Operation Group ◽  
Pull Out

Abstract Background Poor osseointegration is the key reason for implant failure after arthroplasty,whether under osteoporotic or normal bone conditions. To date, osseointegration remains a major challenge. Recent studies have shown that deferoxamine (DFO) can accelerate osteogenesis by activating the hypoxia signaling pathway. The purpose of this study was to test the following hypothesis: after knee replacement, intra-articular injection of DFO will promote osteogenesis and osseointegration with a 3D printed titanium prosthesis in the bones of osteoporotic rats. Materials and methods Ninety female Sprague–Dawley rats were used for the experiment. Ten rats were used to confirm the successful establishment of the osteoporosis model: five rats in the sham operation group and five rats in the ovariectomy group. After ovariectomy and knee arthroplasty were performed, the remaining 80 rats were randomly divided into DFO and control groups (n = 40 per group). The two groups were treated by intraarticular injection of DFO and saline respectively. After 2 weeks, polymerase chain reaction (PCR) and immunohistochemistry were used to evaluate the levels of HIF-1a, VEGF, and CD31. HIF-1a and VEGF have been shown to promote angiogenesis and bone regeneration, and CD31 is an important marker of angiogenesis. After 12 weeks, the specimens were examined by micro-computed tomography (micro-CT), biomechanics, and histopathology to evaluate osteogenesis and osseointegration. Results The results of PCR showed that the mRNA levels of VEGF and CD31 in the DFO group were significantly higher than those in the control group. The immunohistochemistry results indicated that positive cell expression of HIF-1a, VEGF, and CD31 in the DFO group was also higher. Compared with the control group, the micro-CT parameters of BMD, BV/TV, TB. N, and TB. Th were significantly higher. The maximal pull-out force and the bone-to-implant contact value were also higher. Conclusions The local administration of DFO, which is used to activate the HIF-1a signaling pathway, can promote osteogenesis and osseointegration with a prosthesis in osteoporotic bone.

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