scholarly journals N-Acetylcysteine Slows Down Cardiac Pathological Remodeling by Inhibiting Cardiac Fibroblast Proliferation and Collagen Synthesis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Jin Zhou ◽  
Jing Xu ◽  
Shan Sun ◽  
Mengyuan Guo ◽  
Peng Li ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Signaling Pathway ◽  
Collagen Synthesis ◽  
Expression Level ◽  
Control Group ◽  
Myocardial Tissue ◽  
Cardiac Structure ◽  
Sprague Dawley ◽  
Pathological Remodeling

Objective. By observing the effect of N-acetylcysteine (NAC) on the proliferation and collagen synthesis of rat cardiac fibroblasts (CFs) to explore the effect of NAC on cardiac remodeling (CR). Methods. In vivo, first, the Sprague Dawley (SD) rat myocardial hypertrophy model was constructed, and the effect of NAC on cardiac structure and function was detected by echocardiography, serological testing, and Masson staining. Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression level of antioxidant enzymes, and flow cytometry was used to detect the intracellular reactive oxygen species (ROS) content. In vitro, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and 5-ethynyl-2 ′ -deoxyuridine (EdU) staining were used to detect cell proliferation, and the expression level of the NF-κB signaling pathway was detected. Results. Compared with the control group, the model group had disordered cardiac structure, reduced cardiac function, and obvious oxidative stress (OS) response. However, after NAC treatment, it could obviously improve the rat cardiac structure and cardiac function and alleviate redox imbalance and cardiology remodeling. At the same time, NAC can inhibit the activation of the NF-κB signaling pathway and reduce the proliferation level of CFs and the amount of 3H proline incorporated. Conclusions. NAC can inhibit AngII-induced CF proliferation and collagen synthesis through the NF-κB signaling pathway, alleviate the OS response of myocardial tissue, inhibit the fibrosis of myocardial tissue, and thus slow down the pathological remodeling of the heart.

scholarly journals MicroRNA-1297 suppressed the Akt/GSK3β signaling pathway and stimulated neural apoptosis in an in vivo sevoflurane exposure model

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052098210
Author(s):  
Quan Wang ◽  
Jingcong Luo ◽  
Ruiqiang Sun ◽  
Jia Liu
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Neuronal Apoptosis ◽  
In Vitro Model ◽  
Nervous System Development ◽  
Exposure Model ◽  
Control Group ◽  
Pten Protein ◽  
Vitro Model

Objective Common inhalation anesthetics used for clinical anesthesia (such as sevoflurane) may induce nerve cell apoptosis during central nervous system development. Furthermore, anesthetics can produce cognitive impairments, such as learning and memory impairments, that continue into adulthood. However, the precise mechanism remains largely undefined. We aimed to determine the function of microRNA-1297 (miR-1297) in sevoflurane-induced neurotoxicity. Methods Reverse transcription-polymerase chain reaction assays were used to analyze miR-1297 expression in sevoflurane-exposed mice. MTT and lactate dehydrogenase (LDH) assays were used to measure cell growth, and neuronal apoptosis was analyzed using flow cytometry. Western blot analyses were used to measure PTEN, PI3K, Akt, and GSK3β protein expression. Results In sevoflurane-exposed mice, miR-1297 expression was up-regulated compared with the control group. MiR-1297 up-regulation led to neuronal apoptosis, inhibition of cell proliferation, and increased LDH activity in the in vitro model of sevoflurane exposure. MiR-1297 up-regulation also suppressed the Akt/GSK3β signaling pathway and induced PTEN protein expression in the in vitro model. PTEN inhibition (VO-Ohpic trihydrate) reduced PTEN protein expression and decreased the effects of miR-1297 down-regulation on neuronal apoptosis in the in vitro model. Conclusion Collectively, the results indicated that miR-1297 stimulates sevoflurane-induced neurotoxicity via the Akt/GSK3β signaling pathway by regulating PTEN expression.

scholarly journals MiR-206 regulates the progression of osteoporosis via targeting HDAC4

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Zhiyuan Lu ◽  
Dawei Wang ◽  
Xuming Wang ◽  
Jilong Zou ◽  
Jiabing Sun ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Diagnostic Value ◽  
Expression Level ◽  
Luciferase Reporter ◽  
Control Group ◽  
Luciferase Reporter Gene ◽  
Mineral Density ◽  
Gene Assay

Abstract Background More and more studies have confirmed that miRNAs play an important role in maintaining bone remodeling and bone metabolism. This study investigated the expression level of miR-206 in the serum of osteoporosis (OP) patients and explored the effect and mechanism of miR-206 on the occurrence and development of osteoporosis. Methods 120 postmenopausal women were recruited, including 63 cases with OP and 57 women without OP. The levels of miR-206 were determined by qRT-PCR technology. Spearman correlation coefficient was used to evaluate the correlation of miR-206 with bone mineral density (BMD). An ROC curve was used to evaluate the diagnostic value of miR-206 in osteoporosis. The effects of miR-206 on cell proliferation and cell apoptosis of hFOBs were measured by CCK-8 assay and flow cytometry, respectively. Luciferase reporter gene assay was used to confirm the interaction of miR-206 and the 3′UTR of HDAC4. Results Serum miR-206 had low expression level in osteoporosis patient group compared with control group. The expression level of serum miR-206 had diagnostic value for osteoporosis, and the serum miR-206 levels were positively correlated with BMD. The down-regulated miR-206 could inhibit cell proliferation and promote cell apoptosis. Luciferase analysis indicated that HDAC4 was the target gene of miR-206. Conclusions MiR-206 could be used as a new potential diagnostic biomarker for osteoporosis, and in in vitro cell experiments, miR-206 may regulate osteoblast cell proliferation and apoptosis by targeting HDAC4.

scholarly journals Effects of human recombinant growth hormone on exercise capacity, cardiac structure, and cardiac function in patients with adult-onset growth hormone deficiency

2017 ◽  
Vol 45 (6) ◽  
pp. 1708-1719 ◽  
Author(s):  
S Gonzalez ◽  
JD Windram ◽  
T Sathyapalan ◽  
Z Javed ◽  
AL Clark ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Cardiac Function ◽  
Growth Hormone Deficiency ◽  
Exercise Capacity ◽  
Left Ventricular ◽  
Hormone Deficiency ◽  
Control Group ◽  
Cardiac Structure ◽  
Adult Onset ◽  
Risk Of Death

Objective Epidemiological studies suggest that adult-onset growth hormone deficiency (AGHD) might increase the risk of death from cardiovascular causes. Methods This was a 6-month double-blind, placebo-controlled, randomised, cross-over trial followed by a 6-month open-label phase. Seventeen patients with AGHD received either recombinant human growth hormone (rGH) (0.4 mg injection daily) or placebo for 12 weeks, underwent washout for 2 weeks, and were then crossed over to the alternative treatment for a further 12 weeks. Cardiac magnetic resonance imaging, echocardiography, and cardiopulmonary exercise testing were performed at baseline, 12 weeks, 26 weeks, and the end of the open phase (12 months). The results were compared with those of 16 age- and sex-matched control subjects. Results At baseline, patients with AGHD had a significantly higher systolic blood pressure, ejection fraction, and left ventricular mass than the control group, even when corrected for body surface area. Treatment with rGH normalised the insulin-like growth factor 1 concentration without an effect on exercise capacity, cardiac structure, or cardiac function. Conclusion Administration of rGH therapy for 6 to 9 months failed to normalise the functional and structural cardiac differences observed in patients with AGHD when compared with a control group.

The Effect of Gypenosides on Cardiac Function and Expression of Cytoskeletal Genes of Myocardium in Diabetic Cardiomyopathy Rats

2009 ◽  
Vol 37 (06) ◽  
pp. 1059-1068 ◽  
Author(s):  
Min Ge ◽  
Shanfeng Ma ◽  
Liang Tao ◽  
Sudong Guan
Keyword(s):  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Diastolic Pressure ◽  
Pure Water ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Control Group ◽  
Sprague Dawley ◽  
Gene Expressions ◽  
Ventricular Systolic Pressure

The relationship between changes of cardiac function and the gene expressions of two major myocardial skeleton proteins, titin and nebulin, and the effect of gypenosides on these gene expressions in diabetic cardiomyopathy rat were explored in the present study. Forty Sprague-Dawley rats were randomly divided into three groups: control group, diabetic cardiomyopathy group and gypenosides-treated diabetic cardiomyopathy group. The diabetic cardiomyopathy was induced in rats by injecting streptozotocin (STZ, 55 mg/kg) intraperitoneally. Seven weeks after the rats suffered from diabetes, the rats were treated with gypenosides 100 mg/kg per day orally for six weeks in gypenosides-treated group. In the meanwhile, the pure water was given to diabetic cardiomyopathy and the control groups. Subsequently, the cardiac functions, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), ± dP/dtmax and t–dP/dmaxt, as well as the mRNA content and proteins of titin and nebulin in myocardium were determined. The results indicated that (1) the diabetic cardiomyopathy rats had decreased LVSP and ± dP/dtmax, increased LVEDP, and prolonged t–dP/dtmax than normal rats; (2) LVSP and ± dP/dtmax in diabetic cardiomyopathy rats treated with gypenosides were significantly higher and LVEDP and t–dP/dtmax were significantly lower than those without giving gypenosides; (3) the mRNA contents and proteins of titin and nebulin in diabetic cardiomyopathy rats were remarkably lower than those in the control rats and gypenosides had no effect on mRNA and protein expression levels of titin and nebulin in diabetic cardiomyopathy rats. We conclude that (1) the cardiac function as well as the mRNA expressions of titin and nebulin decreased in diabetic cardiomyopathy rats; (2) gypenosides secure cardiac muscles and their function from diabetic impairment and these beneficial effects of gypenosides are not by changing the expressions of titin and nebulin.

scholarly journals Amylase-Producing Maltooligosaccharide Provides Potential Relief in Rats with Loperamide-Induced Constipation

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Eun Yeong Jang ◽  
Yejin Ahn ◽  
Hyung Joo Suh ◽  
Ki-Bae Hong ◽  
Kyungae Jo
Keyword(s):  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Positive Control ◽  
Lactobacillus Bulgaricus ◽  
Control Group ◽  
Sprague Dawley ◽  
Potential Relief ◽  
Bowel Movements ◽  
Mucosal Thickness

Constipation is a chronic disease caused by infrequent, inadequate, and difficult bowel movements. The present study aimed to evaluate the potential laxative effect of maltooligosaccharide (MOS) on loperamide-induced constipation in a rat model. In vitro experiments were conducted to evaluate the effect of MOS on the growth of lactic acid bacteria. Moreover, to examine the effect of MOS administration on Sprague-Dawley (SD) rats with loperamide-induced constipation, the drinking water for the rats was supplemented with 10% or 15% of MOS for 14 days, and, thereafter, the improvement in constipation was assessed. For this, the rats were divided into five groups: normal (Nor), loperamide-induced constipated (Con), positive control (15% of dual-oligosaccharide (DuO-15)), 10% MOS treated (MOS-10), and 15% MOS-treated (MOS-15). In an in vitro test, MOS treatment promoted the growth of lactic acid bacteria except Lactobacillus bulgaricus. Treatment with higher MOS dose relieved constipation in rats by improving the fecal pellet and water content. Furthermore, in the high MOS dose group, the cecal short-chain fatty acid levels significantly increased compared to those in the control group (P<0.001). MOS treatment also improved the mucosal thickness as well as mucin secretion and increased the area of intestinal Cajal cells compared to that in the control group (P<0.001). These findings suggest that MOS relieves constipation and has beneficial effect on the gastrointestinal tract, and, therefore, it can be used as an ingredient in functional foods for treating constipation or improving intestinal health.

scholarly journals Endothelial dysfunction precedes hypertension in diet-induced insulin resistance

1998 ◽  
Vol 275 (3) ◽  
pp. R788-R792 ◽  
Author(s):  
Prasad V. G. Katakam ◽  
Michael R. Ujhelyi ◽  
Margarethe E. Hoenig ◽  
Allison Winecoff Miller
Keyword(s):  
Insulin Resistance ◽  
Endothelial Dysfunction ◽  
Serum Insulin ◽  
Serum Glucose ◽  
Mesenteric Arteries ◽  
Control Group ◽  
Sprague Dawley ◽  
Insulin Resistant ◽  
Glucose Levels

The insulin-resistant (IR) syndrome may be an impetus for the development of hypertension (HTN). Unfortunately, the mechanism by which this could occur is unclear. Our laboratory and others have described impaired endothelium-mediated relaxation in IR, mildly hypertensive rats. The purpose of the current study is to determine if HTN is most likely a cause or result of impaired endothelial function. Sprague-Dawley rats were randomized to receive a fructose-rich diet for 3, 7, 10, 14, 18, or 28 days or were placed in a control group. The control group received rat chow. After diet treatment, animals were instrumented with arterial cannulas, and while awake and unrestrained, their blood pressure (BP) was measured. Subsequently, endothelium-mediated relaxation to acetylcholine was determined (in vitro) by measuring intraluminal diameter of phenylephrine-preconstricted mesenteric arteries (∼250 μM). Serum insulin levels were significantly elevated in all groups receiving fructose feeding compared with control, whereas there were no differences in serum glucose levels between groups. Impairment of endothelium-mediated relaxation starts by day 14 [mean percent maximal relaxation (Emax): 69 ± 10% of baseline] and becomes significant by day 18 (Emax: 52 ± 11% of baseline; P < 0.01). However, the mean BP (mmHg) does not become significantly elevated until day 28 [BP: 132 ± 1 ( day 28) vs. 116 ± 3 (control); P < 0.05]. These findings demonstrate that both IR and endothelial dysfunction occur before HTN in this model and suggest that endothelial dysfunction may be a mechanism linking insulin resistance and essential HTN.

scholarly journals Mechanism of KLF4 Protection against Acute Liver Injury via Inhibition of Apelin Signaling

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Weitao Ji ◽  
Hongyun Shi ◽  
Hailin Shen ◽  
Jing Kong ◽  
Jiayi Song ◽  
...  
Keyword(s):  
Liver Injury ◽  
Signaling Pathway ◽  
Acute Liver Injury ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Protein Levels ◽  
Klf4 Expression ◽  
Mrna And Protein Expression

Krüppel-like factor 4 (KLF4) is a key transcription factor that regulates genes involved in the proliferation or differentiation in different tissues. Apelin plays roles in cardiovascular functions, metabolic disease, and homeostatic disorder. However, the biological function of apelin in liver disease is still ongoing. In this study, we investigated the mechanism of KLF4-mediated protection against acute liver injury via the inhibition of the apelin signaling pathway. Mice were intraperitoneally injected with carbon tetrachloride (CCl4; 0.2 mL dissolved in 100 mL olive oil, 10 mL/kg) to establish an acute liver injury model. A KLF4 expression plasmid was injected through the tail vein 48 h before CCl4 treatment. In cultured LX-2 cells, pAd-KLF4 or siRNA KLF4 was overexpressed or knockdown, and the mRNA and protein levels of apelin were determined. The results showed that the apelin serum level in the CCl4-injected group was higher than that of control group, and the expression of apelin in the liver tissues was elevated while KLF4 expression was decreased in the CCl4-injected group compared to the KLF4-plasmid-injected group. HE staining revealed serious hepatocellular steatosis in the CCl4-injected mice, and KLF4 alleviated this steatosis in the mice injected with KLF4 plasmid. In vitro experiments showed that tumor necrosis factor-alpha (TNF-α) could downregulate the transcription and translation levels of apelin in LX-2 cells and also upregulate KLF4 mRNA and protein expression. RT-PCR and Western blotting showed that the overexpression of KLF4 markedly decreased basal apelin expression, but knockdown of KLF4 restored apelin expression in TNF-α-treated LX-2 cells. These in vivo and in vitro experiments suggest that KLF4 plays a key role in inhibiting hepatocellular steatosis in acute liver injury, and that its mechanism might be the inhibition of the apelin signaling pathway.

scholarly journals The Serum Cell-Free microRNA Expression Profile in MCTD, SLE, SSc, and RA Patients

2020 ◽  
Vol 9 (1) ◽  
pp. 161 ◽  
Author(s):  
Barbara Stypinska ◽  
Anna Wajda ◽  
Ewa Walczuk ◽  
Marzena Olesinska ◽  
Aleksandra Lewandowska ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Signaling Pathway ◽  
Expression Profile ◽  
Mirna Expression ◽  
Lupus Erythematosus ◽  
Connective Tissue Diseases ◽  
Mirna Expression Profile ◽  
Expression Level ◽  
Control Group ◽  
Mirna Expression Level

Mixed connective tissue disease (MCTD) is a rare disorder characterized by symptoms that overlap two or more Autoimmune Connective Tissue Diseases (ACTDs). The aim of this study was to determine whether miRNAs participating in the TLRs signaling pathway could serve as biomarkers differentiating MCTD or other ACTD entities from a healthy control group and between groups of patients. Although the selected miRNA expression level was not significantly different between MCTD and control, we observed that miR-126 distinguishes MCTD patients from all other ACTD groups. The expression level of miRNAs was significantly higher in the serum of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients compared to controls. The miR-145 and -181a levels distinguished RA from other ACDT patients. miR-155 was specific for SLE patients. MiR-132, miR-143, and miR-29a distinguished RA and SLE patients from the systemic sclerosis (SSc) group. Additionally, some clinical parameters were significantly related to the miRNA expression profile in the SLE group. SLE and RA are characterized by a specific serum expression profile of the microRNAs associated with the Toll-like receptors (TLRs) signaling pathway. The analysis showed that their level distinguishes these groups from the control and from other ACTD patients. The present study did not reveal a good biomarker for MCTD patients.

scholarly journals BuPiHeWei Decoction Ameliorates 5-Fu-Induced Intestinal Mucosal Injury in the Rats by Regulating the TLR-4/NF-κB Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Zhi-gao Sun ◽  
Ya-zhuo Hu ◽  
Yu-guo Wang ◽  
Jian Feng ◽  
Yong-qi Dou
Keyword(s):  
Body Weight ◽  
Signaling Pathway ◽  
Bacillus Licheniformis ◽  
Mucosal Injury ◽  
Protective Role ◽  
Inflammatory Factors ◽  
Control Group ◽  
Sprague Dawley ◽  
Intestinal Mucosal Injury ◽  
Group 5

BuPiHeWei (BPHW) decoction, a classic Traditional Chinese Medicinal (TCM) prescription, has been widely used in clinical practice to relieve digestive symptoms caused by chemotherapy, such as diarrhea and vomiting. The present study aimed to investigate whether BPHW decoction exerted a protective role in the 5-Fu-induced intestinal mucosal injury in the rats by regulating the mechanisms of TLR-4/NF-κB signaling pathway. There were 35 Sprague Dawley rats randomly divided into four groups: normal control group, 5-Fu group, 5-Fu + BPHW decoction group (10.5 g/kg, for five continuous days), and 5-Fu + Bacillus licheniformis capsule group (0.2 g/kg, for five continuous days). Animal models were established by intraperitoneal injection of 5-Fu (30 mg/Kg, for five consecutive days). At the end of the treatment period, body weight, diarrhea score, and histological examination were examined. Furthermore, the expression of TLR-4/NF-κB pathway was detected to reveal its mechanism. The results showed that BPHW decoction effectively reduced diarrhea score and increased body weight and height of villi after 5-Fu chemotherapy. In addition, BPHW decoction could significantly inhibit the expression of TLR-4, NF-κB, and inflammatory factors (including TNF-α, IL-1β, and IL-6) in the intestine, and the efficacy was significantly higher than that of Bacillus licheniformis capsule. In summary, BPHW decoction might be considered an effective drug to alleviate intestinal mucosal injury in the rats induced by 5-Fu.

scholarly journals Baicalin improves the in vitro developmental capacity of pig embryos by inhibiting apoptosis, regulating mitochondrial activity and activating sonic hedgehog signaling

2019 ◽  
Vol 25 (9) ◽  
pp. 538-549 ◽  
Author(s):  
Qing Guo ◽  
Mei-Fu Xuan ◽  
Zhao-Bo Luo ◽  
Jun-Xia Wang ◽  
Sheng-Zhong Han ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Signaling Pathway ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Control Group ◽  
Mitochondrial Activity ◽  
Cell Stage ◽  
Shh Signaling ◽  
Developmental Capacity

Abstract Baicalin, a traditional Chinese medicinal monomer whose chemical structure is known, can be used to treat female infertility. However, the effect of baicalin on embryonic development is unknown. This study investigated the effects of baicalin on in vitro development of parthenogenetically activated (PA) and in vitro fertilized (IVF) pig embryos and the underlying mechanisms involved. Treatment with 0.1 μg/ml baicalin significantly improved (P < 0.05) the in vitro developmental capacity of PA pig embryos by reducing the reactive oxygen species (ROS) levels and apoptosis and increasing the mitochondrial membrane potential (ΔΨm) and ATP level. mRNA and protein expression of sonic hedgehog (SHH) and GLI1, which are related to the SHH signaling pathway, in PA pig embryos at the 2-cell stage, were significantly higher in the baicalin-treated group than in the control group. To confirm that the SHH signaling pathway is involved in the mechanism by which baicalin improves embryonic development, we treated embryos with baicalin in the absence or presence of cyclopamine (Cy), an inhibitor of this pathway. Cy abolished the effects of baicalin on in vitro embryonic development. In conclusion, baicalin improves the in vitro developmental capacity of PA and IVF pig embryos by inhibiting ROS production and apoptosis, regulating mitochondrial activity and activating SHH signaling.

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