MicroRNA-34a alleviates steroid-induced avascular necrosis of femoral head by targeting Tgif2 through OPG/RANK/RANKL signaling pathway

The study aims to investigate the effect of microRNA-34a (miR-34a) targeting Tgif2 on steroid-induced avascular necrosis of femoral head (SANFH) by regulating OPG/RANK/RANKL signaling pathway. SD rats were divided into normal control and model (RNAKL rat models) groups. The model group was further assigned into model control, negative control, miR-34a mimics and miR-34a inhibitors groups. QRT-PCR was applied to detect miR-34a, Tgif2, OPG, RANK and RNAKL mRNA expressions. Femoral head tissues were collected for Micro-CT scanning and HE staining. QRT-PCR and Western blotting were used to detect expressions of miR-34a, Tgif2, OPG, RANK, RANKL and Runx2, OPN and OC in bone tissues. Dual-luciferase reporter gene assay was used to testify the target relationship between miR-34a and Tgif2. Compared with the normal control group, the model group showed increased Tgif2, RANK and RANKL mRNA expressions, but decreased miR-34a and OPG mRNA expressions. Tgif2 mRNA expression was negatively correlated with miR-34a and OPG mRNA expressions. Micro-CT showed cystic degeneration of femoral head, with decreased bone volume/total volume (BV/TV), bone surface area/bone volume and trabecular number in the model control group compared with the normal control group. Compared with the model control group, the miR-34a mimics group showed increased BV/TV and trabecular thickness and Runx2, OPN and OC expressions, while the parameters decreased in the miR-34a inhibitors group. Compared with the normal control group, the other groups showed increased Tgif2, RANK and RANKL expressions but decreased miR-34a and OPG expressions. Compared with the model control group, Tgif2, RANK and RANKL expressions decreased and miR-34a and OPG expressions increased in the miR-34a mimics group, while the miR-34a inhibitors group had a reverse trend in contrast to the miR-34a mimics group. Tgif2 is a target gene of miR-34a. In conclusion, miR-34a can alleviate SANFH through targeting Tgif2 and further regulating OPG/RANK/RANKL signaling pathway. Impact statement miR-34a can alleviate SANFH through targeting Tgif2 and further regulating OPG/RANK/RANKL signaling pathway, which can be used as a new theoretical basis for SANFH treatment.

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The Effect of Different Laser Irradiation on Cyclophosphamide-Induced Leucopenia in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/756406 ◽

2014 ◽

Vol 2014 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

Jizhong Zhao ◽

Ke Cheng ◽

Haiping Deng ◽

Ling Zhao ◽

Lanlan Liu ◽

...

Keyword(s):

Laser Irradiation ◽

Normal Control ◽

Sham Group ◽

Control Group ◽

Sham Treatment ◽

Irradiation Group ◽

Model Control ◽

Model Control Group ◽

Wbc Count ◽

First Time

Objective. To assess the effect of different lasers on cyclophosphamide- (CTX-) induced leucopenia in rats.Methods. 11 rats were normal control and 55 rats were injected with a dose of 80 mg/kg CTX for the first time and 40 mg/kg on the 6th and the 11th days to establish a leucopenia model. Rats of the irradiation groups received a 5-minute laser irradiation with either single 10.6 μm or 650 nm laser or alternatively 10.6 μm–650 nm laser irradiation, besides a sham treatment on acupoint Dazhui (DU 14) and acupoint Zusanli (ST 36) of both sides, 8 times for 16 days. Normal and model control group received no treatment.Results. On day 16 after the first CTX injection, the WBC counts from all the laser irradiation groups were significantly higher than those from the model control and the sham group (P<0.05), while there were no significant differences compared with the normal control (P>0.05). The TI of 10.6 μm–650 nm laser irradiation group was significantly higher than that of the model control group (P<0.05).Conclusions. The single and combined 10.6 μm and 650 nm laser irradiation on ST36 and DU14 accelerated the recovery of the WBC count in the rats with leucopenia.

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Improvement of Electroacupuncture on APP/PS1 Transgenic Mice in Spatial Learning and Memory Probably due to Expression of Aβand LRP1 in Hippocampus

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/7603975 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 9

Author(s):

Xin Wang ◽

Yanhuan Miao ◽

Jiawula Abulizi ◽

Fu Li ◽

Yuping Mo ◽

...

Keyword(s):

Learning And Memory ◽

Morris Water Maze ◽

Normal Control ◽

Water Maze ◽

Normal Control Group ◽

Morris Water Maze Test ◽

Control Group ◽

Spatial Learning And Memory ◽

Model Group ◽

Amyloid A

Objectives. To explore the alterations ofβ-amyloid (Aβ) and low density lipoprotein receptor-related protein-1 (LRP1) in APP/PS1 mice after electroacupuncture (EA) treatment and further to explore the mechanism.Methods. Forty 6-month-old APP/PS1 mice were randomly divided into a model group and an EA group, with twenty wild-type mice used as a normal control group. Mice in the EA group were treated with EA at GV 20 (băi huì) and bilateral KI 1 (yŏng quán) acupoints for 6 weeks. The Morris water maze was applied to assess the spatial memory in behavior. Immunohistochemistry (IHC), ELISA, Western blotting, and so forth were used to observe the expression of LRP1 and Aβ.Results. The Morris water maze test showed that, compared with the normal control group, the model group’s learning and memory capabilities were significantly decreased (P<0.05;P<0.01). The EA group was reversed (P<0.05;P<0.01). The hippocampal expression of Aβin the EA group was significantly decreased compared to the model group (P<0.01). The expression of LRP1 in the model group was significantly lower than that in the normal control group (P<0.01); the expression in the EA group was significantly higher than that in the model group (P<0.01).Conclusions. EA therapy can improve the learning and memory capabilities of APP/PS1 mice. The underlying mechanism may lie in the upregulation of an Aβtransport receptor and LRP1.

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Eldecalcitol Plays a Role in Postmenopausal Osteoporosis through Mir-151a-3p/Socs5 Pathway

Tobacco Regulatory Science ◽

10.18001/trs.7.5.1.166 ◽

2021 ◽

Vol 7 (5) ◽

pp. 3934-3941

Author(s):

Hongqing Zhang ◽

Li Jia ◽

Danzhi Li

Keyword(s):

Postmenopausal Osteoporosis ◽

Cell Activity ◽

Control Group ◽

Sham Operation ◽

Model Group ◽

Mineral Density ◽

Specific Mechanism ◽

Sham Operation Group ◽

Model Control ◽

Model Control Group

Objective: This study set out to explore the specific mechanism of Eldecalcitol in postmenopausal osteoporosis (PMOP) and its relationship with miR-151a-3p/SOCS5 pathway. Methods: Forty-five rats were randomly and equally divided into sham operation group (SOG), model control group (MCG) and Eldecalcitol group (EG). miR-151a-3p, SOCS5 and bone mineral density (BMD) levels in each group were detected. MC3T3-E1 cells were modeled and divided into control group (CG), model group (MG) and EG. miR-151a-3p-inhibitor and pcDNA3.1-SOCS were transfected into model cells. miR-151 A-3P, SOCS5, RANKL and OPG levels as well as cell activity of cells in each group were observed. Results: Eldecalcitol intervention in rats can reduce BMD reduction caused by PMOP, reduce the miR-151a-3p level and increase the SOCS5 level. Cell experiments found that Eldecalcitol intervention can improve cell activity, inhibit the miR-151a-3p level and promote the SOCS5 expression, all of which can improve bone resorption of model cells, increase cell activity, inhibit the RANKL level and promote the OPG level. Conclusion: Eldecalcitol plays a role in PMOP by inhibiting miR-151a-3p and promoting the SOCS5 level.

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Boeravinone B promotes fracture healing in ovariectomyinduced osteoporotic rats via the regulation of NF-κB p65/IκB-α/SIRT-1 signaling pathway

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v18i5.7 ◽

2021 ◽

Vol 18 (5) ◽

pp. 955-960

Author(s):

Jianlin Zhang ◽

Longze Zong ◽

Dongyu Bai

Keyword(s):

Fracture Healing ◽

Signaling Pathway ◽

Normal Control ◽

Bone Mineral ◽

Normal Control Group ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Type I ◽

Expression Levels ◽

Tnf Α

Purpose: To investigate the fracture-healing effect of boeravinone B in ovariectomy-induced (OVX) osteoporotic rats. Methods: Adult female Wistar rats (n = 30) were ovariectomized and after three months, the unilateral cross-tibial fractures were fixed with intramedullary nails. The rats were then randomly assigned to three groups of 10 rats each: normal control group, OVX group and 100 mg/kg body weight boeravinone B group. Boeravinone B was orally administered for a period of 5 weeks. The effect of boeravinone B on indices of bone formation and resorption was assessed. Levels of inflammatory cytokines including tumor necrosis factor- α (TNF-α) and interleukin-1β (IL-1β) were determined using enzyme-linked immunosorbent assay (ELISA). Western blotting was used to determine the expression levels of NF-κB p65, IкB-α and SIRT1 proteins. Results: There were significant increases in the activities of tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP), and collagen type I fragment (CTX) level and serum osteocalcin (OC) of OVX group, when compared with normal control group (p < 0.05). However, treatment with boeravinone B significantly reduced the activities and levels of these parameters, relative to OVX group (p < 0.05). The levels of TNF-α and IL-1β significantly increased in OVX group, relative normal control group, but were significantly lower following treatment with boeravinone B (p < 0.05). Bone mineral content (BMC) was not significantly altered in OVX and boeravinone B-treated groups, when compared with normal control group (p > 0.05). There was significant reduction in bone mineral density (BMD) of OVX group relative to normal control group (p < 0.05). However, treatment with boeravinone B significantly increased the BMD, when compared with OVX group (p < 0.05). After Week 5 of treatment, boeravinone B significantly enhanced bone remodeling and formation of callus. Treatment with boeravinone B significantly reduced the expression levels of NF-κB p65 and IκB-α proteins, and significantly upregulated the expression of SIRT-1 (p < 0.05). Conclusion: The results obtained in this study suggest that boeravinone B promotes the healing of fracture caused by osteoporosis via a mechanism involving NF-κB p65/IκB-α/SIRT-1 signaling pathway.

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The long non-coding RNA MEG3 plays critical roles in the pathogenesis of cholesterol gallstone

PeerJ ◽

10.7717/peerj.10803 ◽

2021 ◽

Vol 9 ◽

pp. e10803

Author(s):

Changlin Qian ◽

Weiqing Qiu ◽

Jie Zhang ◽

Zhiyong Shen ◽

Hua Liu ◽

...

Keyword(s):

Normal Control ◽

Regulatory Network ◽

Cholesterol Gallstone ◽

Normal Control Group ◽

Differentially Expressed ◽

Pcr Analysis ◽

Control Group ◽

Ppi Network ◽

Model Group ◽

Qrt Pcr

Background Cholesterol gallstone (CG) is the most common gallstone disease, which is induced by biliary cholesterol supersaturation. The purpose of this study is to investigate the pathogenesis of CG. Methods Sixteen mice were equally and randomly divided into model group and normal control group. The model group was fed with lithogenic diets to induce CG, and then gallbladder bile lipid analysis was performed. After RNA-seq library was constructed, differentially expressed mRNAs (DE-mRNAs) and differentially expressed lncRNAs (DE-lncRNAs) between model group and normal control group were analyzed by DESeq2 package. Using the cluster Profiler package, enrichment analysis for the DE-mRNAs was carried out. Based on Cytoscape software, the protein-protein interaction (PPI) network and competing endogenous RNA (ceRNA) network were built. Using quantitative real-time reverse transcription-PCR (qRT-PCR) analysis, the key RNAs were validated. Results The mouse model of CG was suc cessfully established, and then 181 DE-mRNAs and 33 DE-lncRNAs between model and normal groups were obtained. Moreover, KDM4A was selected as a hub node in the PPI network, and lncRNA MEG3 was considered as a key lncRNA in the regulatory network. Additionally, the miR-107-5p/miR-149-3p/miR-346-3-MEG3 regulatory pairs and MEG3-PABPC4/CEP131/NUMB1 co-expression pairs existed in the regulatory network. The qRT-PCR analysis showed that KDM4A expression was increased, and the expressions of MEG3, PABPC4, CEP131, and NUMB1 were downregulated. Conclusion These RNAs might be related to the pathogenesis of CG.

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Corn silk polysaccharide ameliorates high fat diet induced hepatic steatosis in mice

E3S Web of Conferences ◽

10.1051/e3sconf/202127103027 ◽

2021 ◽

Vol 271 ◽

pp. 03027

Author(s):

Wang Tailin ◽

Wang Zhiwen ◽

Liu Yi ◽

Huang Li

Keyword(s):

Food Intake ◽

Normal Control ◽

High Fat Diet ◽

Statistical Significance ◽

Normal Control Group ◽

Control Group ◽

Model Group ◽

High Fat ◽

Corn Silk ◽

Intake Water

To study the therapeutic effect of corn silk polysaccharide (CSP) on NAFLD mice induced by high fat diet. C57BL/6J mice were divided into normal control group (NC), high fat diet (HFD) group, HFD+200 mg/kg CSP group, and HFD+600 mg/kg CSP group. NAFLD mouse model was established by HFD feeding. Blood and liver tissues of each group were collected and biochemical and pathological tests were performed. The energy intake of NAFLD model group was higher than that of normal control group, and the food intake, water intake, and excretion of NAFLD model group were lower than that of normal control group. There was no statistical significance in the food intake, energy intake, water intake, and excretion of CSP group compared with that of NAFLD model group, nor was there any statistical significance between CSP and two doses of CSP. Biochemical tests showed that CSP decreased the levels of alanine aminotransferase, aspartate aminotransferase, triglyceride and total cholesterol in serum of HFDfed mice, and inhibited the expressions of IL-6 and TNF-α in liver tissue. Pathological results showed that CSP improved HFD-induced hepatic steatosis.

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The long non-coding RNA MEG3 plays critical roles in the pathogenesis of cholesterol gallstone

10.21203/rs.3.rs-16206/v1 ◽

2020 ◽

Author(s):

Changlin Qian ◽

Hua Liu ◽

Weijing Qiu ◽

Jie Zhang ◽

Zhiyong Shen ◽

...

Keyword(s):

Normal Control ◽

Regulatory Network ◽

Cholesterol Gallstone ◽

Gallstone Disease ◽

Lipid Hydroperoxide ◽

Normal Control Group ◽

Differentially Expressed ◽

Control Group ◽

Ppi Network ◽

Model Group

Abstract Background: Cholesterol gallstone (CG) is the most common gallstone disease, which is induced by biliary cholesterol supersaturation. The purpose of this study is to investigate the pathogenesis of CG. Methods: Sixteen mice were equally and randomly divided into model group and normal control group. The model group was fed with lithogenic diets to induce CG, and then gallbladder bile lipid analysis was performed. After RNA-seq library was constructed, differentially expressed mRNAs (DE-mRNAs) and differentially expressed lncRNAs (DE-lncRNAs) between model group and normal control group were analyzed by DESeq2 package. Using clusterProfiler package, enrichment analysis for the DE-mRNAs was carried out. Based on Cytoscape software, the protein-protein interaction (PPI) network and competing endogenous RNA (ceRNA) network were built. Results: The mouse model of CG was successfully established, and then 181 DE-mRNAs and 33 DE-lncRNAs between model and normal groups were selected. For the down-regulated SCP2 , lipid hydroperoxide transport was enriched. Moreover, KDM4A was selected as a hub node in the PPI network, and MEG3 was taken as a key lncRNA in the regulatory network. Additionally, the miR-107-5p/miR-149-3p/miR-346-3p—MEG3 regulatory pairs and MEG3—PABPC4/CEP131/NUMB1 co-expression pairs existed in the regulatory network. Conclusion: These RNAs might be related to the pathogenesis of CG.

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Effect of Angiotensin 1-7 on Myocardial Calcium Pump in Salt-Sensitive Hypertensive Rats

Journal of Clinical Medicine Research ◽

10.32629/jcmr.v2i3.455 ◽

2021 ◽

Vol 2 (3) ◽

Author(s):

Jun Cao ◽

Qianfeng Jiang ◽

Mingliang Fang

Keyword(s):

Normal Control ◽

Early Stage ◽

Sensory Nerve ◽

Normal Control Group ◽

Calcium Pump ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Model Group ◽

Plasma Membrane Atpase ◽

Hypertensive Rats

Objective — To investigate the effects of angiotensin 1-7 (Ang1-7) on plasma membrane ATPase isoform 1 (PMCA1) in salt-sensitive hypertensive rats. Methods — Thirty newborn male Wistar rats were selected to establish the salt-sensitive hypertensive rat model with sensory nerve injury, which were then randomly divided into 5 groups (n=5), including model group, Telmisartan group, Ramipril group, Ang1-7 group, and A-779 group. Another normal control group was established (n=5). After 4 weeks of intervention, the tail blood pressure of rats in each group was measured, and then the apical tissue of left ventricle was cut. The contents of AngⅡ and Ang1-7 in cardiomyocytes were detected by enzyme-linked immunosorbent assay. The expression of PMCA1 mRNA and protein in heart of salt-sensitive hypertensive rats were detected by RT-PCR and immunohistochemistry. Results — (1) Compared with the normal control group, the concentration of AngⅡ in the myocardium of salt-sensitive hypertensive rats increased (P < 0.05), which decreased after the intervention of Telmisartan and Ramipril (P < 0.05), and no change occurred after the intervention of Ang1-7 in concentration (P＞0.05). (2) Compared with the normal control group, the concentration of myocardial Ang1-7 in salt-sensitive hypertensive rats decreased (P < 0.05), and increased after the intervention of telmisartan and ramipril (P < 0.05), and increased after the intervention of A-779 (P < 0.05). (3) The expression of PMCA1 mRNA and protein in salt-sensitive hypertensive rats was increased compared with the normal control group (P < 0.05), and the expression of Ang-(1-7), telmisartan and ramipril was decreased compared with the model group (P < 0.05). The expression of p38MAPK mRNA and p-p38MAPK protein in the myocardium of salt-sensitive hypertensive rats was increased compared with that in the normal control group (P < 0.05), and the expression of Ang-(1-7), Telmisartan and Ramipril was decreased compared with that in the model group (P < 0.05). Conclusion — Ang-(1-7) may be involved in the regulation of cardiac calcium pump, inhibiting its overcompensation and delaying the occurrence of calcium pump inhibition in the early stage of salt-sensitive hypertension. Ang-(1-7) can inhibit the activity of p38MAPK and protect the heart, and its regulation on PMCA1 may be mediated by the expression of p38MAPK pathway.

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Study of Guanxinning Injection on Regulatory Mechanism of Bcl-2 and Bax by Liquid Nitrogen Freezing-Mediated Femoral Head Necrosis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/4540124 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Xiaofeng Zhang ◽

Xilin Xu ◽

Gerhard Litscher ◽

Zemin Sheng ◽

Lu Wang ◽

...

Keyword(s):

Femoral Head ◽

Liquid Nitrogen ◽

Normal Control ◽

Blood Stasis ◽

Normal Control Group ◽

Femoral Head Necrosis ◽

Prolonged Treatment ◽

Control Group ◽

The Third ◽

The Impact

The objective of this study was to investigate the impact of femoral head perfusion by traditional Chinese medicine Guanxinning injection promoting blood circulation for removing blood stasis on the expression of Bcl-2 and Bax induced by liquid nitrogen freezing-mediated femoral head necrosis. 90 rabbits were randomized into three groups. Normal control group was not subjected to any medication. Saline and Guanxinning group were perfused with 0.9% saline and Guanxinning injection once every three days through the hip joint, respectively. Six animals in each group were sacrificed at weeks 1, 3, 6, 9, and 12. PCR and Western blot measured the expressions of Bcl-2 and Bax in the femoral head. The bax expression in the Guanxinning group reduced at the third week significantly compared to the normal control group (P<0.01). The Bcl-2 expression in the Guanxinning group increased substantially at the third week (P<0.05 or P<0.01). Prolonged treatment elevated the expression of Bcl-2 in the Guanxinning group while that of Bax reduced remarkably (P<0.01). Moreover, the ratio of Bcl-2 to Bax increased gradually in the Guanxinning group with prolonged drug administration. Guanxinning injection can inhibit the cell apoptosis of femoral head necrosis through the treatment by femoral head perfusion.

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Study on potential differentially expressed genes in stroke by bioinformatics analysis

Neurological Sciences ◽

10.1007/s10072-021-05470-1 ◽

2021 ◽

Author(s):

Xitong Yang ◽

Pengyu Wang ◽

Shanquan Yan ◽

Guangming Wang

Keyword(s):

Gene Expression ◽

Differentially Expressed Genes ◽

Normal Control ◽

Enrichment Analysis ◽

Normal Control Group ◽

Control Group ◽

Ppi Network ◽

Hub Genes ◽

Pathway Enrichment ◽

Key Genes

AbstractStroke is a sudden cerebrovascular circulatory disorder with high morbidity, disability, mortality, and recurrence rate, but its pathogenesis and key genes are still unclear. In this study, bioinformatics was used to deeply analyze the pathogenesis of stroke and related key genes, so as to study the potential pathogenesis of stroke and provide guidance for clinical treatment. Gene Expression profiles of GSE58294 and GSE16561 were obtained from Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) were identified between IS and normal control group. The different expression genes (DEGs) between IS and normal control group were screened with the GEO2R online tool. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were performed. Using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and gene set enrichment analysis (GSEA), the function and pathway enrichment analysis of DEGS were performed. Then, a protein–protein interaction (PPI) network was constructed via the Search Tool for the Retrieval of Interacting Genes (STRING) database. Cytoscape with CytoHubba were used to identify the hub genes. Finally, NetworkAnalyst was used to construct the targeted microRNAs (miRNAs) of the hub genes. A total of 85 DEGs were screened out in this study, including 65 upward genes and 20 downward genes. In addition, 3 KEGG pathways, cytokine − cytokine receptor interaction, hematopoietic cell lineage, B cell receptor signaling pathway, were significantly enriched using a database for labeling, visualization, and synthetic discovery. In combination with the results of the PPI network and CytoHubba, 10 hub genes including CEACAM8, CD19, MMP9, ARG1, CKAP4, CCR7, MGAM, CD79A, CD79B, and CLEC4D were selected. Combined with DEG-miRNAs visualization, 5 miRNAs, including hsa-mir-146a-5p, hsa-mir-7-5p, hsa-mir-335-5p, and hsa-mir-27a- 3p, were predicted as possibly the key miRNAs. Our findings will contribute to identification of potential biomarkers and novel strategies for the treatment of ischemic stroke, and provide a new strategy for clinical therapy.

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