scholarly journals Autophagy Suppresses Invasiveness of Endometrial Cells through Reduction of Fascin-1

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaomei Luo ◽  
Wei Cheng ◽  
Shizhang Wang ◽  
Zhihong Chen ◽  
Jieqiong Tan
Keyword(s):  
Metabolic Diseases ◽  
Growth Curves ◽  
Cellular Growth ◽  
Control Group ◽  
Scratch Assay ◽  
Endometrial Cells ◽  
Autophagy Inhibitor ◽  
Exogenous Expression ◽  
Potential Therapeutics

Objective. Autophagy has been reported to be involved in the development of various disorders such as neurodegenerative and metabolic diseases and tumors. Autophagy activators and inhibitors are also potential therapeutics for these diseases. However, the mechanism of autophagic involvement in different diseases is not the same, and the role of autophagy in endometriosis (EM) has not yet been elucidated. This research investigated the mechanism by which autophagy acts in EM, with the aim of establishing a theoretical basis for its prevention and treatment through the targeted interference with autophagy. Methods. We used an RNA interference fragment targeting ATG5, the autophagy activator rapamycin, and the autophagy inhibitor 3-MA or overexpression of filopodia-related protein fascin-1, in conjunction with clonogenic assays, growth curves, and scratch assay to investigate the influence of autophagy on cellular growth, proliferation, and invasiveness. We collected specimens from 20 clinical cases of EM and investigated the protein expression of the autophagic marker LC3-II, the autophagic substrate p62, and fascin-1. Results. Rapamycin was able to inhibit the proliferation and colony formation of the endometriotic cell line CRL-7566, whereas the autophagy inhibitor 3-MA as well as the interference with the autophagy-related gene ATG5 had the opposite effect. More importantly, the autophagy activator rapamycin was able to inhibit the growth of filopodia in the endometriotic cells, and the overexpression of the fascin-1 restored the rapamycin-induced decrease of invasiveness. We found that the expression of the autophagy marker LC3-II was significantly reduced among the clinical EM specimens compared to the control group, while the expressions of fascin-1 and autophagic substrate p62 were increased. Conclusion. Our results indicate that the inhibition of autophagy and exogenous expression of fascin-1 may promote the invasiveness of endometrial cells. As a corollary, autophagy represents a potential target for the treatment of EM.

ATI-2341 Trifluoroacetic Acid (TFA) Promotes Menstrual Blood-Derived Mesenchymal Stem Cell Recruitment and Enhances Uterine Repair Through Gi Pathway in Asherman’s Syndrome

2022 ◽  
Vol 12 (3) ◽  
pp. 506-513
Author(s):  
Ying Lv ◽  
Liyan Ye ◽  
Xiujuan Zheng
Keyword(s):  
Menstrual Blood ◽  
Control Group ◽  
Dependent Manner ◽  
Asherman’S Syndrome ◽  
Expression Levels ◽  
Endometrial Cells ◽  
Injury Model ◽  
Recruitment Effect ◽  
Dose Dependent

This study aimed to explore the role of ATI-2341 in Asherman’s syndrome and its impact on menstrual blood-derived mesenchymal stem cells (MenSCs). Following establishment of endometrial injury model, MenSCs were extracted from rats and cultured. They were treated with ATI-2341 TFA at different concentrations (10 ng/mL, 50 ng/mL, 100 ng/mL) and MenSCs treated without ATI-2341 TFA were taken as controls. Flow cytometry was conducted to detect the cell cycle. MTT was carried out to evaluate proliferation of endometrial cells. The expression levels of MMP-9, TIMP-1, CK, and VIM were determined with staining used to reflect morphology of endometrium. Administration with ATI-2341 TFA resulted in decreased expression of MMP-9 and increased expression of TIMP-1 in a dose-dependent manner. Of note, the increase of ATI-2341 TFA concentration was accompanied with elevated cell proliferation rate, increased number of glands in the endometrium, and decreased fibrosis area. As treated with 100 ng/mL ATI-2341 TFA, the cells exhibited more glands than that under other concentrations with uniformly arranged glands and lowest expression levels of CK and VIM, control group had plenty of blue-stained collagen fibers in the intima and least amount of glands. ATI-2341 TFA 100 ng/mL induced endometrial epithelial recruitment effect on MenSCs and promoted endometrial repair more significantly than Gi-3 pathway agonists. Collectively, ATI-2341 TFA enhances MenSC recruitment and facilitates endometrial epithelial cells proliferation and the repair of uterine damage in Asherman’s syndrome through Gi pathway. These findings provide a\ novel insight into the MenSC-based treatment against Asherman’s syndrome and deserve further investigation.

scholarly journals Synthetic glabridin derivatives mitigate steatohepatitis in a diet-induced biopsy-confirmed non-alcoholic steatosis hepatitis mouse model through paraoxonase-2

2021 ◽  
Author(s):  
Gu-Choul Shin ◽  
Hyeong Min Lee ◽  
Na Yeon Kim ◽  
Sang-Ku Yoo ◽  
Yun Sun Park ◽  
...  
Keyword(s):  
Antioxidant Defense ◽  
Hepatic Cirrhosis ◽  
Metabolic Diseases ◽  
Antioxidant Defense System ◽  
Therapeutic Effects ◽  
Biological Functions ◽  
Defense System ◽  
Cellular Target ◽  
Potential Therapeutics

AbstractLimited therapeutic agents have been developed for non-alcoholic steatohepatitis (NASH), a common immunometabolic disease that can progress to hepatic cirrhosis and cancer. Glabridin and its derivatives are potential therapeutics for some metabolic diseases. However, the therapeutic effects of glabridin and its derivatives on NASH and their biological functions are unclear. This study demonstrated the role of synthetic glabridin derivatives (SGDs) in alleviating hepatic steatosis and inflammation in a biopsy-confirmed rodent NASH model. SGDs exerted therapeutic effects by activating autophagy and the antioxidant defense system, which mitigate NASH pathogenesis. The cellular target of HSG4112, an SGD, was paraoxonase 2. These findings will enable the development of novel therapeutics for NASH in the future.

scholarly journals Potential Prognostic Role of Immune System Activation Marker Neopterin in Patients with Type 2 Diabetes

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Songül Ünüvar ◽  
Zübeyde Tanrıverdi ◽  
Hamza Aslanhan
Keyword(s):  
Type 2 Diabetes ◽  
Bacterial Infections ◽  
Metabolic Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Serum Neopterin ◽  
Immune System Activation ◽  
Study Results

Summary Background: An increase in neopterin concentrations is known in some pathologies due to interferon-gamma (INF-γ) activation. These include viral and bacterial infections, auto immune diseases, metabolic diseases, psychiatric disorders, tissue and organ rejections, and different malignancies. The aim of this study was to evaluate the role of neopterin as a prognostic biomarker in type 2 diabetes, which is a metabolic disease with a high worldwide prevalence. Methods: The study included a total of one hundred thirty-nine individuals including one hundred and six patients admitted to a family medicine outpatient clinic and diagnosed with type 2 diabetes and thirty-three healthy volunteers. Serum neopterin concentrations were measured using the enzyme-linked immunosorbent assay. Results: Serum neopterin levels significantly increased in type 2 diabetes patients, compared to the control group (p<0.00001). Conclusions: Early diagnosis of diabetes and determination of the appropriate therapeutic options are of utmost importance, as diabetes is also associated with other systemic diseases. The risk of developing secondary diseases is high in untreated patients. Our study results suggest that serum neopterin may be a useful biomarker in patients with type 2 diabetes.

scholarly journals What is the role of profibrogenic and proinflammatory factors in developing atrial fibrillation associated with metabolic syndrome components?

2021 ◽  
Vol 26 (11) ◽  
pp. 4752
Author(s):  
V. A. Ionin ◽  
E. I. Barashkova ◽  
V. A. Pavlova ◽  
G. I. Borisov ◽  
K. A. Averchenko ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Metabolic Syndrome ◽  
Abdominal Obesity ◽  
Healthy Subjects ◽  
Metabolic Diseases ◽  
Inflammatory Biomarkers ◽  
Control Group ◽  
Galectin 3 ◽  
Laboratory Investigations

Aim. To determine the concentration of blood fibrotic and inflammatory biomarkers in patients with atrial fibrillation (AF) associated with metabolic syndrome (MS) components.Material and methods. The study included 646 patients aged 35-65 years: patients with AF and MS (n=142), those with AF and without MS (n=113), those with MS and without AF (n=175) and the control group consisted of healthy subjects without cardiovascular and metabolic diseases (n=107). All participants underwent anthropometric and laboratory investigations. Profibrogenic (aldosterone, galectin-3, TGF-beta1, CTGF) and proinflammatory (CT-1, IL-6) factors were determined in serum and plasma by ELISA. Statistical analysis was performed using IBM SPSS Statistics software (version 22.0).Results. The highest concentrations of fibrotic and inflammatory biomarkers were found in patients with AF in combination with MS. In MS patients without AF, the concentration of aldosterone, galectin-3, TGF-beta1, CTGF, CT-1, and IL-6 was also higher than in healthy subjects. The levels of aldosterone, CT-1 and IL-6 in patients with AF were higher in the presence of three or more MS components, while the highest values of these parameters were found in patients with five MS components. The lowest concentrations of galectin-3, CTGF, and CT-1 in patients with AF were found in patients without MS components, and in the presence of even 1 MS component, they were significantly higher. Correlation analysis made it possible to establish a stronger relationship between aldosterone and TGF-betal with systolic blood pressure (p=0,493, p<O,O001 and p=0,530, p<O,O001), and CT-1, CTGF and IL-6 in a greater degree correlated with waist circumference (p=0,563, p<0,0001; p=0,626, p<0,0001; p=0,480, p<O,O001). The concentrations of galectin-3 and CTGF were more positively correlated with an increase in the number of MS components. In patients with AF and hypertension (HTN), but without abdominal obesity (AO), higher values of aldosterone (108,1±70,3 pg/ml and 89,3±32,2 pg/ml, p=0,003) and TGF-beta1 (3680,1±1863,3 pg/ml and 1968,1±1611,5 pg/ml, p=0,015) in serum than in AF patients without HTN and without AO. In the group of patients with AF and AO, but without HTN, higher concentrations of IL-6 (2,9±0,7 pg/ml and 1,9±0,6 pg/ml, p=0,001) and CTGF (162,9±92,2 pg/ml and 116,3±63,4 pg/ml, p=0,0001).Conclusion. It can be assumed that hypertension through the aldosterone system and TGF-beta1, as well as abdominal obesity through the cytokine system CT-1 and IL-6 activate various mechanisms and pathways for myocardial remodeling. Integral molecules galectin-3 and CTGF mediate their interactions, in particular in patients with a combination of several MS components and contribute to a higher AF risk.

A new look at endometriosis: the role of restoring of full immune surveillance over ectopic cells of the endometrium

2017 ◽  
pp. 99-106
Author(s):  
S.M. Melnikov ◽  
◽  
O.F. Tatskyy ◽  
Keyword(s):  
Clinical Symptoms ◽  
Immune Surveillance ◽  
Hormonal Treatment ◽  
Regulatory Peptides ◽  
Control Group ◽  
Immune Homeostasis ◽  
Childbearing Age ◽  
Endometrial Cells ◽  
Immunological Disorders

The article deals with the role of immunological disorders in the occurrence of genital endometriosis recurrences, as well as the results of treatment of this disease. The objective: the study of the effect of restoring immune homeostasis with the help of exogenous peptides on the effectiveness of the treatment of endometriosis. Patients and methods. Endometriosis was treated in 68 women of childbearing age. In 48 patients, uterine endometriosis (adenomyosis) was diagnosed, and 20 cases were endometriosis of the vaginal part of the cervix. In order to study the effectiveness of Camelyn-Bio in the treatment of endometriosis, patients were divided into two groups. Results. In the group of patients who were prescribed hormonal monotherapy, 3 months after the end of the course of hormonal treatment, recurrence of endometriosis was observed. They arose due to systemic and local immunological disorders, which probably led to ectopic endometrial cells from immune surveillance. Due to the properties of the exogenous peptides of the Camelyn-Bio preparation, reacting with the regulatory peptides of the ectopic cells of the endometrium, there are conditions for a complete immunological surveillance of the endometrium foci. In the group of patients treated with Camelyn-Bio, the incidence of relapse was 4 times lower than that of the control group. Conclusion. Treatment of endometriosis with the combined progestogen and estragon drug is effective and contributes to a sustained regression of the clinical symptoms of the disease. A break in the use of basic hormonal therapy leads to relapses of endometriosis, which is confirmed by the instrumental methods of research. Clinical experience confirms that the restoration of the immune homeostasis of patients with the Camelyn-Bio preparation is an important factor in increasing the effectiveness of endometriosis treatment, leads to clinical remission and improves the quality of life. Key words: endometriosis, ectopic cells of the endometrium, apoptosis, Camelyn-Bio, immune homeostasis, relapses, treatment.

scholarly journals Potential Prognostic Role of Immune System Activation Marker Neopterin in Patients with Type 2 Diabetes

2018 ◽  
Vol 37 (4) ◽  
pp. 465-469 ◽  
Author(s):  
Songül Ünüvar ◽  
Zübeyde Tanrıverdi ◽  
Hamza Aslanhan
Keyword(s):  
Type 2 Diabetes ◽  
Bacterial Infections ◽  
Metabolic Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Serum Neopterin ◽  
Immune System Activation ◽  
Study Results

Summary Background: An increase in neopterin concentrations is known in some pathologies due to interferon-gamma (INF-γ) activation. These include viral and bacterial infections, auto immune diseases, metabolic diseases, psychiatric disorders, tissue and organ rejections, and different malignancies. The aim of this study was to evaluate the role of neopterin as a prognostic biomarker in type 2 diabetes, which is a metabolic disease with a high worldwide prevalence. Methods: The study included a total of one hundred thirtynine individuals including one hundred and six patients admitted to a family medicine outpatient clinic and diagnosed with type 2 diabetes and thirty-three healthy volunteers. Serum neopterin concentrations were measured using the enzyme-linked immunosorbent assay. Results: Serum neopterin levels significantly increased in type 2 diabetes patients, compared to the control group (p<0.001). Conclusions: Early diagnosis of diabetes and determination of the appropriate therapeutic options are of utmost importance, as diabetes is also associated with other systemic diseases. The risk of developing secondary diseases is high in untreated patients. Our study results suggest that serum neopterin may be a useful biomarker in patients with type 2 diabetes.

scholarly journals Association Between rs12037447, rs146732504, rs151078858, rs55723436, and rs6094136 Polymorphisms and Kawasaki Disease in the Population of Polish Children

2021 ◽  
Vol 9 ◽  
Author(s):  
Piotr Buda ◽  
Maciej Chyb ◽  
Anna Smorczewska-Kiljan ◽  
Anna Wieteska-Klimczak ◽  
Agata Paczesna ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Genome Wide Association Study ◽  
Metabolic Diseases ◽  
Developed Countries ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Coronary Artery Involvement ◽  
Genome Wide

Background: Kawasaki disease (KD) is an acute self-limited febrile vasculitis that mainly affects young children. Coronary artery involvement is the most serious complication in children with KD. It is currently the leading cause of acquired cardiac disease in children from developed countries. Literature data indicate a significant role of genetic susceptibility to KD.Objective: The aim of this study was to perform the first Genome-Wide Association Study (GWAS) in a population of Polish children with KD and identify susceptible genes involved in the pathogenesis of KD.Materials and Methods: The blood samples of Kawasaki disease patients (n = 119) were collected between 2016 and 2020, isolated and stored at the Department of Pediatrics, Nutrition and Metabolic Diseases, Children's Memorial Health Institute in Warsaw. The control group was based on Polish donors (n = 6,071) registered as the POPULOUS collection at the Biobank Lab of The Department of Molecular Biophysics in University of Lodz. DNA samples were genotyped for 558,231 Single Nucleotide Polymorphisms (SNPs) using the 24 × 1 Infinium HTS Human Core Exome microarrays according to the protocol provided by the manufacturer. In order to discover and verify genetic risk-factors for KD, association analysis was carried out using PLINK 1.9.Results: Of all 164,395 variants, 5 were shown to occur statistically (padjusted &lt; 0.05) more frequent in Kawasaki disease patients than in controls. Those are: rs12037447 in non-coding sequence (padjusted = 8.329 × 10−4, OR = 8.697, 95% CI; 3.629–20.84) and rs146732504 in KIF25 (padjusted = 0.007354, OR = 11.42, 95% CI; 3.79–34.43), rs151078858 in PTPRJ (padjusted = 0.04513, OR = 8.116, 95% CI; 3.134–21.01), rs55723436 in SPECC1L (padjusted = 0.04596, OR = 5.596, 95% CI; 2.669–11.74), rs6094136 in RPN2 (padjusted = 0.04755, OR = 10.08, 95% CI; 3.385–30.01) genes.Conclusion: Polymorphisms of genes KIF25, PTRPJ, SPECC1L, RNP2 may be linked with the incidence of Kawasaki disease in Polish children.

Tryptophan-Niacin Metabolism in Rat with Puromycin Aminonucleoside-Induced Nephrosis

2006 ◽  
Vol 76 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Yukari Egashira ◽  
Shin Nagaki ◽  
Hiroo Sanada
Keyword(s):  
Body Weight ◽  
Urinary Excretion ◽  
Enzyme Activities ◽  
Treated Group ◽  
Control Group ◽  
Puromycin Aminonucleoside ◽  
Low Level ◽  
Key Enzyme

We investigated the change of tryptophan-niacin metabolism in rats with puromycin aminonucleoside PAN-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan-niacin conversion. PAN-treated rats were intraperitoneally injected once with a 1.0% (w/v) solution of PAN at a dose of 100 mg/kg body weight. The collection of 24-hour urine was conducted 8 days after PAN injection. Daily urinary excretion of nicotinamide and its metabolites, liver and blood NAD, and key enzyme activities of tryptophan-niacin metabolism were determined. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. The kidneyα-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) activity in the PAN-treated group was significantly decreased by 50%, compared with the control group. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. A decrease in urinary excretion of niacin and the conversion of tryptophan to niacin in nephrotic rats may contribute to a low level of blood tryptophan. The role of kidney ACMSD activity may be minimal concerning tryptophan-niacin conversion under this experimental condition.

The Use of Posterior Pericardiotomy Technique to Prevent Postoperative Pericardial Effusion in Cardiac Surgery

2012 ◽  
Vol 15 (2) ◽  
pp. 84 ◽  
Author(s):  
Canturk Cakalagaoglu ◽  
Cengiz Koksal ◽  
Ayse Baysal ◽  
Gokhan Alici ◽  
Birol Ozkan ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Heart Surgery ◽  
Artery Bypass ◽  
Pericardial Tamponade ◽  
Anxiety Level ◽  
Control Group ◽  
Echocardiographic Study ◽  
Number Of Patients ◽  
Hospital Stays

<p><b>Aim:</b> The goal was to determine the effectiveness of the posterior pericardiotomy technique in preventing the development of early and late pericardial effusions (PEs) and to determine the role of anxiety level for the detection of late pericardial tamponade (PT).</p><p><b>Materials and Methods:</b> We divided 100 patients randomly into 2 groups, the posterior pericardiotomy group (n = 50) and the control group (n = 50). All patients undergoing coronary artery bypass grafting surgery (CABG), valvular heart surgery, or combined valvular and CABG surgeries were included. The posterior pericardiotomy technique was performed in the first group of 50 patients. Evaluations completed preoperatively, postoperatively on day 1, before discharge, and on postoperative days 5 and 30 included electrocardiographic study, chest radiography, echocardiographic study, and evaluation of the patient's anxiety level. Postoperative causes of morbidity and durations of intensive care unit and hospital stays were recorded.</p><p><b>Results:</b> The 2 groups were not significantly different with respect to demographic and operative data (<i>P</i> > .05). Echocardiography evaluations revealed no significant differences between the groups preoperatively; however, before discharge the control group had a significantly higher number of patients with moderate, large, and very large PEs compared with the pericardiotomy group (<i>P</i> < .01). There were 6 cases of late PT in the control group, whereas there were none in the pericardiotomy group (<i>P</i> < .05). Before discharge and on postoperative day 15, the patients in the pericardiotomy group showed significant improvement in anxiety levels (<i>P</i> = .03 and .004, respectively). No differences in postoperative complications were observed between the 2 groups.</p><p><b>Conclusion:</b> Pericardiotomy is a simple, safe, and effective method for reducing the incidence of PE and late PT after cardiac surgery. It also has the potential to provide a better quality of life.</p>

The Estimation of prostate specific antigen (PSA) concentrations in patients with prostatitis by fully automated ELISA technique.

2020 ◽  
Vol 3 (11) ◽  
pp. 1100-1104
Author(s):  
Hussein Naeem Aldhaheri ◽  
Ihsan Edan AlSaimary ◽  
Murtadha Mohammed ALMusafer
Keyword(s):  
Personal Information ◽  
Receptor Gene ◽  
Specific Antigen ◽  
Gene Clusters ◽  
Control Group ◽  
P Value ◽  
Group Data ◽  
Elisa Technique ◽  
And Control

      The Aim of this study was to determine Immunogenetic expression of  Toll-like receptor gene clusters related to prostatitis, to give acknowledge about Role of TLR in prostatitis immunity in men from Basrah and Maysan provinces. A case–control study included 135 confirmed prostatitis patients And 50 persons as a control group. Data about age, marital status, working, infertility, family history and personal information like (Infection, Allergy, Steroid therapy, Residency, Smoking, Alcohol Drinking, Blood group, Body max index (BMI) and the clinical finding for all patients of Prostatitis were collected. This study shows the effect of PSA level in patients with prostatitis and control group, with P-value <0.0001 therefore the study shows a positive significant between elevated PSA levels and Prostatitis.

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