scholarly journals Proteomic and Functional Analyses Reveal That Kallikrein 6 Enhances Communicating Hydrocephalus by Injuring Neuronal Synapses

2021 ◽  
Author(s):  
Lei Yuan ◽  
Dongdong Zou ◽  
Xia Yang ◽  
Xin Chen ◽  
Youming Lu ◽  
...  
Keyword(s):  
Rat Model ◽  
Differentially Expressed ◽  
Control Group ◽  
Communicating Hydrocephalus ◽  
Loss Of Function ◽  
Neuronal Nuclei ◽  
Neuronal Synapses ◽  
Hoechst Staining ◽  
Synaptic Structures ◽  
Kallikrein 6

Abstract Communicating hydrocephalus (CH) is a common neurological disorder caused by a blockage of cerebrospinal fluid. In this study, we aimed to explore the potential molecular mechanism underlying CH development. Quantitative proteomic analysis was performed to screen the differentially expressed proteins (DEPs) between patients with and without CH. A CH rat model was verified by Hoechst staining, and the co-localization of the target protein and neuron was detected using immunofluorescence staining. Loss-of-function experiments were performed to examine the effect of KLK6 on the synapse structure. A total of 11 DEPs were identified, and kallikrein 6 (KLK6) expression was found to be significantly upregulated in patients with CH compared with that in patients without CH. The CH rat model was successfully constructed, and KLK6 was found to be co-localized with neuronal nuclei in brain tissue. The expression level of KLK6 in the CH group was higher than that in the control group. After interference of KLK6 expression, the expression levels of synapsin-1 and PSD95 in neuronal cells were increased, and the length, number, and structure of synapses were significantly improved. The transcriptome profile (PRJNA719985) after interference of KLK6 expression was obtained, and 5,681 differentially expressed genes (DEGs) were identified. The upregulated DEGs of Appl2, Nav2, and Nrn1 may be involved in the recovery of synaptic structures after interference of KLK6 expression. Collectively, KLK6 participates in the development of CH and might provide a new target for CH treatment.

scholarly journals Proteomics and functional study reveal kallikrein-6 enhances communicating hydrocephalus

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Lei Yuan ◽  
Dongdong Zou ◽  
Xia Yang ◽  
Xin Chen ◽  
Youming Lu ◽  
...  
Keyword(s):  
Rat Model ◽  
Differentially Expressed ◽  
Functional Study ◽  
Control Group ◽  
Communicating Hydrocephalus ◽  
Loss Of Function ◽  
Neuronal Nuclei ◽  
Hoechst Staining ◽  
Interfering Rna ◽  
Kallikrein 6

Abstract Background Communicating hydrocephalus (CH) is a common neurological disorder caused by a blockage of cerebrospinal fluid. In this study, we aimed to explore the potential molecular mechanism underlying CH development. Methods Quantitative proteomic analysis was performed to screen the differentially expressed proteins (DEPs) between patients with and without CH. A CH rat model was verified by Hoechst staining, and the co-localization of the target protein and neuron was detected using immunofluorescence staining. Loss-of-function experiments were performed to examine the effect of KLK6 on the synapse structure. Results A total of 11 DEPs were identified, and kallikrein 6 (KLK6) expression was found to be significantly upregulated in patients with CH compared with that in patients without CH. The CH rat model was successfully constructed, and KLK6 was found to be co-localized with neuronal nuclei in brain tissue. The expression level of IL-1β, TNF-α, and KLK6 in the CH group was higher than that in the control group. After knockdown of KLK6 expression using small-interfering RNA (siRNA), the expression levels of synapsin-1 and PSD95 in neuronal cells were increased, and the length, number, and structure of synapses were significantly improved. Following siRNA interference KLK6 expression, 5681 differentially expressed genes (DEGs) were identified in transcriptome profile. The upregulated DEGs of Appl2, Nav2, and Nrn1 may be involved in the recovery of synaptic structures after the interference of KLK6 expression. Conclusions Collectively, KLK6 participates in the development of CH and might provide a new target for CH treatment.

scholarly journals Restorative potential of (−)-epicatechin in a rat model of Gulf War illness muscle atrophy and fatigue

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Israel Ramirez-Sanchez ◽  
Viridiana Navarrete-Yañez ◽  
Alejandra Garate-Carrillo ◽  
Modesto Lara-Hernandez ◽  
Judith Espinosa-Raya ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Rat Model ◽  
Inflammatory Cytokine ◽  
Gulf War ◽  
Plasma Metabolites ◽  
Control Group ◽  
Loss Of Function ◽  
Gulf War Illness ◽  
Mediators Of Inflammation ◽  
Male Wistar Rats

AbstractWe examined in a rat model of Gulf War illness (GWI), the potential of (−)-epicatechin (Epi) to reverse skeletal muscle (SkM) atrophy and dysfunction, decrease mediators of inflammation and normalize metabolic perturbations. Male Wistar rats (n = 15) were provided orally with pyridostigmine bromide (PB) 1.3 mg/kg/day, permethrin (PM) 0.13 mg/kg/day (skin), DEET 40 mg/kg/day (skin) and were physically restrained for 5 min/day for 3 weeks. A one-week period ensued to fully develop the GWI-like profile followed by 2 weeks of either Epi treatment at 1 mg/kg/day by gavage (n = 8) or water (n = 7) for controls. A normal, control group (n = 15) was given vehicle and not restrained. At 6 weeks, animals were subjected to treadmill and limb strength testing followed by euthanasia. SkM and blood sampling was used for histological, biochemical and plasma pro-inflammatory cytokine and metabolomics assessments. GWI animals developed an intoxication profile characterized SkM atrophy and loss of function accompanied by increases in modulators of muscle atrophy, degradation markers and plasma pro-inflammatory cytokine levels. Treatment of GWI animals with Epi yielded either a significant partial or full normalization of the above stated indicators relative to normal controls. Plasma metabolomics revealed that metabolites linked to inflammation and SkM waste pathways were dysregulated in the GWI group whereas Epi, attenuated such changes. In conclusion, in a rat model of GWI, Epi partially reverses detrimental changes in SkM structure including modulators of atrophy, inflammation and select plasma metabolites yielding improved function.

scholarly journals Restorative Effects of (-)-Epicatechin in a Rat Model of Gulf War Illness Muscle Atrophy and Fatigue

2021 ◽  
Author(s):  
Israel Ramirez-Sanchez ◽  
Viridiana Navarrrete ◽  
Alejandra Garate-Carrillo ◽  
Modesto Lara-Hernandez ◽  
Judith Espinosa-Raya ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Rat Model ◽  
Inflammatory Cytokine ◽  
Gulf War ◽  
Plasma Metabolites ◽  
Control Group ◽  
Loss Of Function ◽  
Gulf War Illness ◽  
Mediators Of Inflammation ◽  
Male Wistar Rats

Abstract We examined in a rat model of Gulf War illness (GWI), the potential of (-)-epicatechin (Epi) to reverse skeletal muscle (SkM) atrophy and dysfunction, decrease mediators of inflammation and normalize metabolic perturbations. Male Wistar rats (n = 15) were provided orally with pyridostigmine bromide (PB) 1.3 mg/kg/day, permethrin (PM) 0.13 mg/kg/day (skin), DEET 40 mg/kg/day (skin) and were physically restrained for 5 min/day for 3 weeks. A one-week period ensued to fully develop the GWI-like profile followed by 2 weeks of either Epi treatment at 1 mg/kg/day by gavage (n = 8) or water (n = 7) for controls. A normal, control group (n = 15) was given vehicles and not restrained. At 6 weeks, animals were subjected to treadmill and limb strength testing followed by euthanasia. SkM and blood sampling was used for histological, biochemical and plasma pro-inflammatory cytokine and metabolomics assessments. GWI animals developed an intoxication profile characterized SkM atrophy and loss of function accompanied by increases in modulators of muscle atrophy, degradation markers and plasma pro-inflammatory cytokine levels. Treatment of GWI animals with Epi yielded either a significant partial or full normalization of the above stated indicators relative to normal controls. Plasma metabolomics revealed that metabolites linked to inflammation and SkM waste pathways were dysregulated in the GWI group whereas Epi, attenuated such changes. In conclusion, in a rat model of GWI, Epi reverses detrimental changes in SkM structure including modulators of atrophy, inflammation and select plasma metabolites yielding improved function.

scholarly journals Analysis of Circulating microRNA Signatures and Preeclampsia Development

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1003
Author(s):  
Margarita L. Martinez-Fierro ◽  
Idalia Garza-Veloz
Keyword(s):  
Pregnant Women ◽  
Expression Profiling ◽  
Gene Prediction ◽  
Microrna Expression ◽  
Differentially Expressed ◽  
Control Group ◽  
Case Group ◽  
Circulating Microrna ◽  
Activated T Cells ◽  
Serum Microrna

microRNAs are important regulators of cell processes and have been proposed as potential preeclampsia biomarkers. We evaluated serum microRNA expression profiling to identify microRNAs involved in preeclampsia development. Serum microRNA expression profiling was evaluated at 12, 16, and 20 weeks of gestation (WG), and at the time of preeclampsia diagnosis. Two groups were evaluated using TaqMan low-density array plates: a control group with 18 normotensive pregnant women and a case group with 16 patients who developed preeclampsia during the follow-up period. Fifty-three circulating microRNAs were differentially expressed between groups (p < 0.05). Compared with controls, hsa-miR-628-3p showed the highest relative quantity values (at 12 WG = 7.7 and at 20 WG = 3.45) and the hsa-miRs -151a-3p and -573 remained differentially expressed from 16 to 20 WG (p < 0.05). Signaling pathways including cancer-related, axon guidance, Neurotrophin, GnRH, VEGF, and B/T cell receptor, were most commonly altered. Further target gene prediction revealed that nuclear factor of activated T-cells 5 gene was included among the transcriptional targets of preeclampsia-modulated microRNAs. Specific microRNAs including hsa-miRs -628-3p, -151a-3p, and -573 were differentially expressed in serum of pregnant women before they developed preeclampsia compared with controls and their participation in the preeclampsia development should be considered.

scholarly journals Systemic Administration of G-CSF Accelerates Bone Regeneration and Modulates Mobilization of Progenitor Cells in a Rat Model of Distraction Osteogenesis

2021 ◽  
Vol 22 (7) ◽  
pp. 3505
Author(s):  
Flavy Roseren ◽  
Martine Pithioux ◽  
Stéphane Robert ◽  
Laure Balasse ◽  
Benjamin Guillet ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Progenitor Cells ◽  
Distraction Osteogenesis ◽  
Rat Model ◽  
Late Phase ◽  
Control Group ◽  
Bone Lengthening ◽  
Hematopoietic Stem ◽  
Osteoblast Activity ◽  
Positron Emission

Granulocyte colony-stimulating factor (G-CSF) was shown to promote bone regeneration and mobilization of vascular and osteogenic progenitor cells. In this study, we investigated the effects of a systemic low dose of G-CSF on both bone consolidation and mobilization of hematopoietic stem/progenitor cells (HSPCs), endothelial progenitor cells (EPCs) and mesenchymal stromal cells (MSCs) in a rat model of distraction osteogenesis (DO). Neovascularization and mineralization were longitudinally monitored using positron emission tomography and planar scintigraphy. Histological analysis was performed and the number of circulating HSPCs, EPCs and MSCs was studied by flow cytometry. Contrary to control group, in the early phase of consolidation, a bony bridge with lower osteoclast activity and a trend of an increase in osteoblast activity were observed in the distracted callus in the G-CSF group, whereas, at the late phase of consolidation, a significantly lower neovascularization was observed. While no difference was observed in the number of circulating EPCs between control and G-CSF groups, the number of MSCs was significantly lower at the end of the latency phase and that of HSPCs was significantly higher 4 days after the bone lengthening. Our results indicate that G-CSF accelerates bone regeneration and modulates mobilization of progenitor cells during DO.

scholarly journals CircHIPK3 regulates the autophagy and apoptosis of hypoxia/reoxygenation-stimulated cardiomyocytes via the miR-20b-5p/ATG7 axis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zhimei Qiu ◽  
Yan Wang ◽  
Weiwei Liu ◽  
Chaofu Li ◽  
Ranzun Zhao ◽  
...  
Keyword(s):  
Cell Injury ◽  
Ischemia Reperfusion ◽  
Circular Rna ◽  
Control Group ◽  
Loss Of Function ◽  
Cardiomyocyte Autophagy ◽  
Myocardial Ischemia Reperfusion ◽  
Injury Research ◽  
Hypoxia Reoxygenation

AbstractAutophagy and apoptosis are involved in myocardial ischemia/reperfusion (I/R) injury. Research indicates that circular RNA HIPK3 (circHIPK3) is crucial to cell autophagy and apoptosis in various cancer types. However, the role of circHIPK3 in the regulation of cardiomyocyte autophagy and apoptosis during I/R remains unknown. Our study aimed to examine the regulatory effect of circHIPK3 during myocardial I/R and investigate its mechanism in cardiomyocyte autophagy and apoptosis. Methods and results. The expression of circHIPK3 was upregulated during myocardial I/R injury and hypoxia/reoxygenation (H/R) injury of cardiomyocytes. To study the potential role of circHIPK3 in myocardial H/R injury, we performed gain-of-function and loss-of-function analyses of circHIPK3 in cardiomyocytes. Overexpression of circHIPK3 significantly promoted H/R-induced cardiomyocyte autophagy and cell injury (increased intracellular reactive oxygen species (ROS) and apoptosis) compared to those in the control group, while silencing of circHIPK3 showed the opposite effect. Further research found that circHIPK3 acted as an endogenous miR-20b-5p sponge to sequester and inhibit miR-20b-5p activity, resulting in increased ATG7 expression. In addition, miR-20b-5p inhibitors reversed the decrease in ATG7 induced by silencing circHIPK3. Conclusions. CircHIPK3 can accelerate cardiomyocyte autophagy and apoptosis during myocardial I/R injury through the miR-20b-5p/ATG7 axis. These data suggest that circHIPK3 may serve as a potential therapeutic target for I/R.

scholarly journals Target identification of hepatic fibrosis using Pien Tze Huang based on mRNA and lncRNA

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jinhang Zhu ◽  
Di Zhang ◽  
Ting Wang ◽  
Zhiliang Chen ◽  
Luan Chen ◽  
...  
Keyword(s):  
Liver Injury ◽  
Hepatic Fibrosis ◽  
Drug Targets ◽  
Enrichment Analysis ◽  
Inflammatory Cells ◽  
Differentially Expressed ◽  
Control Group ◽  
Traditional Chinese Herbal Medicine ◽  
Hepatic Diseases ◽  
Pien Tze Huang

AbstractHepatic fibrosis is a spontaneous wound-healing response triggered by chronic liver injury. Pien Tze Huang (PZH), a traditional Chinese herbal medicine, has been widely used to treat various hepatic diseases in Asia. We used a CCl4-induced mouse model to establish a PZH group of hepatic fibrosis mice treated with PZH and a control group of hepatic fibrosis mice without any treatment. We performed RNA-seq and mass spectrometry sequencing to investigate the mechanism of the PZH response in hepatic fibrosis and identified multiple differentially expressed transcripts (DETs) and proteins (DEPs) that may be drug targets of PZH. Liver functional indices, including serum albumin (ALB), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were significantly decreased in the PZH treatment group (P < 0.05) in the eighth week. Hematoxylin–eosin (HE), Masson and Sirius red staining demonstrated that PZH significantly inhibited infiltration of inflammatory cells and collagen deposition. A total of 928 transcripts and 138 proteins were differentially expressed in PZH-treated mice compared to the control group. Gene Ontology (GO) enrichment analysis suggested that PZH may alleviate liver injury and fibrosis by enhancing the immune process. Taken together, our results revealed that multiple DETs and DEPs may serve as drug targets of PZH in hepatic fibrosis patient in future clinical practice.

scholarly journals PSVII-2 Differentially expressed genes and their biological function in skeletal muscle of calves born from cows with or without protein supplementation during mid-gestation

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 165-166
Author(s):  
Elisa B Carvalho ◽  
Letícia P Sanglard ◽  
Karolina B Nascimento ◽  
Javier M Meneses ◽  
Daniel R Casagrande ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Differentially Expressed Genes ◽  
Muscle Development ◽  
Negative Binomial ◽  
Muscle Protein ◽  
Basal Diet ◽  
Protein Supplementation ◽  
Differentially Expressed ◽  
Control Group ◽  
Q Value

Abstract Gestating cows have an increased nutrient demand to meet the needs of developing the fetus and the mid-gestation is a critical period for the fetal skeletal muscle development. The aim of this study was to evaluate the skeletal muscle transcriptome in the progeny as a function of the maternal protein nutrition during mid-gestation. Eleven Tabapuã cows and their male calves were used in this study. In the first third of gestation (0 to 100 days of gestation; dg), all cows were kept on pasture. From 100 to 200 dg, the control group (CTRL; 7 animals) received a basal diet achieving 5.5% crude protein (CP), whereas the supplemented group (SUPPL; 4 animals) received a basal diet plus protein supplementation (40% CP). After 200 dg, all animals received the same diet. Weaning was performed at 205 ± 7.5 days of age and animals were kept on pasture until reaching 240 days of age, when they were transferred to a feedlot. Muscle samples were collected at 260 days of age and RNA was extracted for RNA-seq analysis. Gene expression data was analyzed with a negative binomial model to identify (q-value ≤ 0.05) differentially expressed genes (DEG) between treatments. A total of 716 DEG were identified (289 DEG up-regulated and 427 down-regulated in SUPPL group; q-value ≤ 0.05). From the 10 most significant down-regulated DEG in the SUPPL group, two genes associated with apoptotic process were identified: MAPK8IP1 and GRINA, with log2 Fold-Changes (log2FC) of 1.04 and 0.49, respectively. From the 10 most significant up-regulated DEG in the SUPPL group, mTOR was identified, with log2FC=0.31. This is a well-known gene involved in muscle protein synthesis. In conclusion, maternal protein supplementation during mid-gestation affects the expression of genes related to energy metabolism and muscle development, which can lead to long-term impacts on production efficiency.

Construction and Evaluation of a Rat Model of Postpartum Fatigue

2021 ◽  
pp. 1-9
Author(s):  
Ting Bai ◽  
Fan Wu ◽  
Shuhan Yan ◽  
Feng Zhang ◽  
Xujuan Xu
Keyword(s):  
Lactic Acid ◽  
Rat Model ◽  
Water Maze ◽  
Acid Level ◽  
Model Building ◽  
Small Sample ◽  
Control Group ◽  
Lactic Acid Level ◽  
Physical Fatigue ◽  
Postpartum Fatigue

<b><i>Objectives:</i></b> The aim of the study was to construct and evaluate a rat model of postpartum fatigue. <b><i>Design:</i></b> This is an article about animal model building. <b><i>Methods:</i></b> Sprague-Dawley rats on the 1st day after delivery were randomized into control group and fatigue group. The deep sleep of rats was interfered with by forcing them to stand in water, to make the rats experience mental and physical fatigue. To maintain galactosis and lactation, rats and pups were caged for 90 min after every 3 h of separation. The control group was separated routinely without any stimulus. The model was evaluated from mental and physical fatigue on the 8th day and 15th day. The mental fatigue was evaluated by a water maze test and the rat’s 5-hydroxytryptamine (5-HT) level in hippocampus, while the physical fatigue was evaluated using lactic acid level in serum and duration of weight-loaded forced swimming. <b><i>Results:</i></b> Among the 7-day and 14-day modeling groups, compared with the control group, the success rate of water maze landing was significantly decreased, the time for water maze landing was significantly prolonged and 5-HT level in hippocampus significantly decreased in the fatigue group. With respect to physical fatigue, among the 7-day and 14-day modeling groups, the lactic acid level in serum in the fatigue group was significantly increased, and the duration of exhaustive swimming of rats was significantly shortened. <b><i>Limitations:</i></b> A small sample size was the main limitation of this study. <b><i>Conclusions:</i></b> We have successfully constructed a rat model of postpartum fatigue by forcing postpartum rats to stand in water, which was similar to a level of stress that contributes to the development of postpartum fatigue. Our model opens the door for future studies evaluating the effectiveness of pharmacological and behavioral therapies.

Abstract 320: End-Tidal Carbon Dioxide Can Guide Fluid Resuscitation in a Cecal Ligation and Puncture Induced Rat Model of Sepsis

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Jing Xu ◽  
Guanghui Zheng ◽  
Liangliang Wu ◽  
Xiangshao Fang ◽  
Yue Wang ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Survival Time ◽  
Fluid Resuscitation ◽  
Rat Model ◽  
Cecal Ligation ◽  
Control Group ◽  
Cecal Ligation And Puncture ◽  
End Tidal Carbon Dioxide ◽  
Lactate Levels ◽  
End Tidal

Introduction: Abnormal levels of end-tidal carbon dioxide (ETCO 2 ) may reflect a derangement in perfusion, metabolism, or gas exchange. It is unclear if ETCO 2 can be used for fluid resuscitation (FR) compared with traditional mean arterial pressure (MAP) as an outcome predictor in sepsis. Hypothesis: Use of ETCO2 is better than MAP in guiding fluid resuscitation to improve lactate levels and microcirculatory blood flow in sepsis. Methods: Thirty-five male Sprague-Dawley rats weighing 350-400g were randomized to: 1) SHAM, n=5; 2) cecal ligation and puncture (CLP) Control group (with CLP, without FR, n=10); 3) ETCO 2 group (with CLP, FR began when ETCO 2 ≤25 mmHg, n=10) and 4) MAP group (with CLP, FR began when MAP≤100 mmHg, n=10). Lactate level, cardiac output (CO), perfused small vessel density (PSVD) and sublingual microvascular flow index (MFI) was assessed at baseline, 2 h, 4 h, 8 h, 10 h and 12 h post-CLP. Survival duration was recorded. Results: After FR,CO in the ETCO 2 group increased compared with the MAP group 12h after CLP while lactate levels decreased compared with the Control and MAP groups (p<0.05) (Figure-1). Both sublingual PSVD and MFI decreased after CLP in the control group and MAP group but significantly improved in the ETCO 2 group 8h post-CLP. The average survival time in the ETCO 2 group was significantly greater than MAP group (Figure-2). Conclusions: ETCO 2 guided FR was associated with improved CO, lactate, microcirculatory flow, and survival time compared to MAP guided FR in a CLP-induced rat model of sepsis.

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