Pharmacological inhibition of EZH2 by GSK126 decreases atherosclerosis by modulating foam cell formation and monocyte adhesion in apolipoprotein E-deficient mice

xlomafota13 shared this article with you from Inoreader Pharmacological inhibition of EZH2 by GSK126 decreases atherosclerosis by modulating foam cell formation and monocyte adhesion in apolipoprotein E-deficient mice Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):841. doi: 10.3892/etm.2021.10273. Epub 2021 Jun 6. ABSTRACT Histone modifications play an important role in the occurrence and development of atherosclerosis in human and atherosclerosis-prone mice. Histone methylation in macrophages, monocytes and endothelial cells markedly influence the progression of atherosclerosis. However, it remains unclear whether treatment with a histone methyltransferase enhancer of zeste homolog 2 (EZH2) inhibitor may suppress atherosclerosis. The present study aimed to determine the effects of the EZH2 inhibitor, GSK126, on the suppression and regression of atherosclerosis in apolipoprotein E-deficient mouse models. In vitro, it was found that pharmacological inhibition of EZH2 by GSK126 markedly reduced lipid transportation and monocyte adhesion during atherogenesis, predominantly through increasing the expression levels of ATP-binding cassette transporter A1 and suppres sing vascular cell adhesion molecule 1 in human THP-1 cells. In vivo, it was found that atherosclerotic plaques in GSK126-treated mice were significantly decreased when comparing with the vehicle-treated animals. These results indicated that the GSK126 has the ability to attenuate the progression of atherosclerosis by reducing macrophage foam cell formation and monocyte adhesion in cell and mouse models. In conclusion, the present study provided new insights into the molecular mechanism behind the action of GSK126 and suggested its therapeutic potential for the treatment of atherosclerosis. PMID:34149887 | PMC:PMC8210282 | DOI:10.3892/etm.2021.10273 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Protective role and molecular mechanism of action of Nesfatin-1 against high glucose-induced inflammation, oxidative stress and apoptosis in retinal epithelial cells

xlomafota13 shared this article with you from Inoreader Protective role and molecular mechanism of action of Nesfatin-1 against high glucose-induced inflammation, oxidative stress and apoptosis in retinal epithelial cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):833. doi: 10.3892/etm.2021.10265. Epub 2021 Jun 3. ABSTRACT Diabetic retinopathy (DR) is a major complication of diabetes mellitus that may cause severe visual impairment. It has been reported that the levels of nesfatin-1 in the serum and vitreous humor were negatively correlated with DR; however, its role in DR has not been fully elucidated. Therefore, the present study was performed to investigate the effect of nesfatin-1 on high glucose-treated human retinal epithelial cells (ARPE-19) and explore the underlying mechanism. The effects of nesfatin-1 on cell viability, inflammation, oxidative stress and apoptosis were examined under high glucose conditions. The Cell Counting Kit-8 assay was used to determine cell viability. The levels of inflammatory cytokines were evaluated using ELISA kits. The reactive oxygen species and malondialdehyde content was estimated using commercial assay kits. Flow cytometry w as performed to detect apoptotic cells and western blot analysis was employed to evaluate the expression of apoptosis-associated proteins. Moreover, the levels of NF-κB, NACHT, LRR and PYD domains-containing protein 3 (NLRP3) and high-mobility group protein B1 (HMGB1) were determined via western blot analysis. The results revealed that nesfatin-1 enhanced cell viability and suppressed inflammation, oxidative stress and apoptosis in the presence of high glucose concentration. Moreover, the activation of the NF-κB/NLRP3 inflammasome signaling and the expression of HMGB1 were inhibited by nesfatin-1. Furthermore, HMGB1 overexpression partially abrogated the inactivation of the NF-κB/NLRP3 inflammasome pathway caused by nesfatin-1. Taken together, these findings demonstrated that nesfatin-1 inhibited the activation of the NF-κB/NLRP3 inflammasome signaling via modulating HMGB1 and exerted a protective effect on ARPE-19 cells against high glucose-induced inflammation, oxidative stres s and apoptosis. PMID:34149879 | PMC:PMC8200809 | DOI:10.3892/etm.2021.10265 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Inhibitory effects of quercetin and its major metabolite quercetin-3-O-β-D-glucoside on human UDP-glucuronosyltransferase 1A isoforms by liquid chromatography-tandem mass spectrometry

xlomafota13 shared this article with you from Inoreader Inhibitory effects of quercetin and its major metabolite quercetin-3-O-β-D-glucoside on human UDP-glucuronosyltransferase 1A isoforms by liquid chromatography-tandem mass spectrometry Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):842. doi: 10.3892/etm.2021.10274. Epub 2021 Jun 6. ABSTRACT Quercetin is a flavonoid that is widely present in plant-derived food. Quercetin-3-O-β-D-glucoside (Q3GA) is a predominant metabolite of quercetin in animal and human plasma. The inhibitory effects of the UDP-glucuronosyl transferases (UGTs) caused by herbal components may be a key factor for the clinical assessment of herb-drug interactions (HDIs). The present study aimed to investigate the inhibitory profile of quercetin and Q3GA on recombinant UGT1A isoforms in vitro. The metabolism of the nonspecific substrate 4-methylumbelliferone (4-MU) by the UGT1A isoforms was assessed by liquid chromatography-tandem mass spectrometry. Preliminary screening experiments indicated that quercetin exhibited stronger inhibitory effects on UGT1A1, UGT1A3, UGT1A6 and UGT1A9 enzymes than Q3GA. Kinetic experiments were performed to characterize the type of i nhibition caused by quercetin and Q3GA towards these UGT isoforms. Quercetin exerted non-competitive inhibition on UGT1A1 and UGT1A6, with half maximal inhibitory concentration (IC50) values of 7.47 and 7.07 µM and inhibition kinetic parameter (Ki) values of 2.18 and 28.87 µM, respectively. Quercetin also exhibited competitive inhibition on UGT1A3 and UGT1A9, with IC50 values of 10.58 and 2.81 µM and Ki values of 1.60 and 0.51 µM, respectively. However, Q3GA displayed weak inhibition on UGT1A1, UGT1A3 and UGT1A6 enzymes with IC50 values of 45.21, 106.5 and 51.37 µM, respectively. In the present study, quercetin was a moderate inhibitor of UGT1A1 and UGT1A3, a weak inhibitor of UGT1A6, and a strong inhibitor on UGT1A9. The results of the present study suggested potential HDIs that may occur following quercetin co-administration with drugs that are mainly metabolized by UGT1A1, UGT1A3 and UGT1A9 enzymes. PMID:34149888 | PMC:PMC8210293 | DOI:10.3892/etm.2021.10274 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

lncRNA ZFAS1 promotes the ox-LDL induced proliferation, invasion and migration of vascular smooth muscle cells

xlomafota13 shared this article with you from Inoreader lncRNA ZFAS1 promotes the ox-LDL induced proliferation, invasion and migration of vascular smooth muscle cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):835. doi: 10.3892/etm.2021.10267. Epub 2021 Jun 4. ABSTRACT Atherosclerosis is a chronic progressive inflammatory vascular disease. The dysfunction of vascular smooth muscle cells (VSMCs) induced by oxidized low-density lipoprotein (ox-LDL) contributes to the formation of atherosclerotic lesions. Additionally, upregulation of the long non-coding RNA zinc finger antisense 1 (ZFAS1) was observed in the plaques of patients with atherosclerosis. The aim of the present study was to explore the functional role of ZFAS1 in atherosclerosis progression. Reverse transcription-quantitative PCR was performed to analyze ZFAS1 mRNA expression, and western blotting was performed to determine the protein expression levels of Ki67, proliferating cell nuclear antigen (PCNA), matrix metallopeptidase (MMP)2 and MMP9. The Cell Counting Kit-8 assay was used to test cell viability. Finally, wound healing and Transwell chamber ass ays were performed to evaluate cell migration and invasion, respectively. The current findings demonstrated that ZFAS1 expression was upregulated by ox-LDL stimulation in VSMCs. Moreover, ZFAS1 overexpression promoted the ox-LDL-induced proliferation, migration and invasion of VSMCs, and upregulated the expression levels of proteins associated with cellular proliferation (Ki67 and PCNA), migration and invasion (MMP2 and 9). By contrast, ZFAS1-knockdown inhibited the proliferation, migration and invasion of VSMCs, and suppressed cell proliferation-, migration- and invasion-associated protein expression. In conclusion, ZFAS1 promoted the ox-LDL-induced proliferation, invasion and migration of VSMCs. Thus, ZFAS1 may represent a novel biomarker for dysfunction of VSMCs in the pathological condition of atherosclerosis. PMID:34149881 | PMC:PMC8200810 | DOI:10.3892/etm.2021.10267 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Primary intratracheal schwannoma misdiagnosed as severe asthma in an adolescent: A case report

paythelady.612 shared this article with you from Inoreader Primary intratracheal schwannoma misdiagnosed as severe asthma in an adolescent: A case report Μέσω pubmed: "world j clin cases"... World J Clin Cases. 2021 Jun 16;9(17):4388-4394. doi: 10.12998/wjcc.v9.i17.4388. ABSTRACT BACKGROUND: Primary intratracheal schwannoma is an extremely rare type of benign airway tumor, especially in adolescents. The presenting symptoms are typically prolonged cough and wheezing that can be misdiagnosed as asthma in adolescent patients. CASE: A 16-year-old adolescent girl admitted to a local hospital with symptoms of an irritating cough and wheezing was diagnosed with bronchial asthma and treated with budesonide and formoterol. Over the next year, the patient's wheezing and coughing symptoms gradually worsened and the antiasthma treatment was ineffective. One week prior to this admission, the patient developed dyspnea after catching a cold and was transferred to our hospital with a diagnosis of severe asthma. However, chest computed tomography and bronchoscopy showed a mass in the trachea. Primary intratracheal schwannoma was diag nosed by biopsy. Her symptoms were relieved by endoscopic resection by electrosurgical snaring combined with argon plasma coagulation. No relapse occurred during an 18 mo follow-up. CONCLUSION: Primary intratracheal schwannoma should be considered in the differential diagnosis in adolescents with recurrent asthma-like attacks. PMID:34141805 | PMC:PMC8173418 | DOI:10.12998/wjcc.v9.i17.4388 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Self-perceived burden and influencing factors in patients with cervical cancer administered with radiotherapy

paythelady.612 shared this article with you from Inoreader Self-perceived burden and influencing factors in patients with cervical cancer administered with radiotherapy Μέσω pubmed: "world j clin cases"... World J Clin Cases. 2021 Jun 16;9(17):4188-4198. doi: 10.12998/wjcc.v9.i17.4188. ABSTRACT BACKGROUND: Cervical cancer is the fourth commonest malignancy in women around the world. It represents the second most commonly diagnosed cancer in South East Asian women, and an important cancer death cause in women of developing nations. Data collected in 2018 revealed 5690000 cervical cancer cases worldwide, 85% of which occurred in developing countries. AIM: To assess self-perceived burden (SPB) and related influencing factors in cervical cancer patients undergoing radiotherapy. METHODS: Patients were prospectively included by convenient sampling at The Fifth Affiliated Hospital of Sun Yat-Sen University, China between March 2018 and March 2019. The survey was completed using a self-designed general information questionnaire, the SPB scale for cancer patients, and the self-care self-efficacy scale, Strategies Used by People to Pro mote Health, which were delivered to patients with cervical cancer undergoing radiotherapy. Measurement data are expressed as the mean ± SD. Enumeration data are expressed as frequencies or percentages. Caregivers were the spouse, offspring, and other in 46.4, 40.9, and 12.7%, respectively, and the majority were male (59.1%). As for pathological type, 90 and 20 cases had squamous and adenocarcinoma/adenosquamous carcinomas, respectively. Stage IV disease was found in 12 (10.9%) patients. RESULTS: A total of 115 questionnaires were released, and five patients were excluded for too long evaluation time (n = 2) and the inability to confirm the questionnaire contents (n = 3). Finally, a total of 110 questionnaires were collected. They were aged 31-79 years, with the 40-59 age group being most represented (65.4% of all cases). Most patients were married (91.8%) and an overwhelming number had no religion (92.7%). Total SPB score was 43.13 ± 16.65. SPB was associated with the place of residence, monthly family income, payment method, transfer status, the presence of radiotherapy complications, and the presence of pain (P < 0.05). The SPB and self-care self-efficacy were negatively correlated (P < 0.01). In multivariate analysis, self-care self-efficacy, place of residence, monthly family income, payment method, degree of radiation dermatitis, and radiation proctitis were influencing factors of SPB (P < 0.05). CONCLUSION: Patients with cervical cancer undergoing radiotherapy often have SPB. Self-care self-efficacy scale, place of residence, monthly family income, payment method, and radiation dermatitis and proctitis are factors independently influencing SPB. PMID:34141781 | PMC:PMC8173433 | DOI:10.12998/wjcc.v9.i17.4188 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Prenatal diagnosis of cor triatriatum sinister associated with early pericardial effusion: A case report

paythelady.612 shared this article with you from Inoreader Prenatal diagnosis of cor triatriatum sinister associated with early pericardial effusion: A case report Μέσω pubmed: "world j clin cases"... World J Clin Cases. 2021 Jun 16;9(17):4395-4399. doi: 10.12998/wjcc.v9.i17.4395. ABSTRACT BACKGROUND: Cor triatriatum sinistrum or cor triatriatum sinister is a rare congenital heart disease that accounts for approximately 0.1% of all cardiac abnormalities. It is defined as the presence of an anomalous septum that divides the left atrium into two cavities, and in most cases, it can be asymptomatic or less frequently very severe. CASE SUMMARY: A 37-year-old pregnant woman visited our hospital. In the first trimester scan, we detected signs of fluid in the pericardium (pericardial effusion) that reached the atriums. In the third trimester, an anomalous septum in the left atrium suspicious of cor triatriatum sinister was detected. Expectant management was decided, the pregnancy evolved normally and resulted in uncomplicated delivery of a healthy child. The findings in the prenatal scan were confirmed by echocardiography and the diag nosis of cor triatriatum sinister was confirmed. The newborn was asymptomatic at all times. CONCLUSION: We show expectant management of cor triatriatum sinister and suggest an association between this entity and early pericardial effusion. PMID:34141806 | PMC:PMC8173403 | DOI:10.12998/wjcc.v9.i17.4395 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Bone marrow inhibition induced by azathioprine in a patient without mutation in the thiopurine S-methyltransferase pathogenic site: A case report

paythelady.612 shared this article with you from Inoreader Bone marrow inhibition induced by azathioprine in a patient without mutation in the thiopurine S-methyltransferase pathogenic site: A case report Μέσω pubmed: "world j clin cases"... World J Clin Cases. 2021 Jun 16;9(17):4230-4237. doi: 10.12998/wjcc.v9.i17.4230. ABSTRACT BACKGROUND: Azathioprine (AZA) and its close analog 6-mercaptopurine are thiopurines widely used in the treatment of patients with cancer, organ transplantation, and autoimmune or inflammatory diseases, including systemic lupus erythematosus. Bone marrow inhibition is a common side effect of AZA, and severe bone marrow inhibition is related to decreased thiopurine S-methyltransferase (TPMT) activity. CASE SUMMARY: We herein report a patient with proliferative lupus nephritis who was using AZA for maintenance therapy, had no common TPMT pathogenic site mutations, and exhibited severe bone marrow inhibition on the 15th day after oral administration. CONCLUSION: This report alerts physicians to the fact that even though the TPMT gene has no common pathogenic site mutation, severe myelosuppression may also o ccur. PMID:34141785 | PMC:PMC8173432 | DOI:10.12998/wjcc.v9.i17.4230 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Pulmonary alveolar proteinosis complicated with tuberculosis: A case report

paythelady.612 shared this article with you from Inoreader Pulmonary alveolar proteinosis complicated with tuberculosis: A case report Μέσω pubmed: "world j clin cases"... World J Clin Cases. 2021 Jun 16;9(17):4400-4407. doi: 10.12998/wjcc.v9.i17.4400. ABSTRACT BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by the accumulation of phospholipoproteinaceous material in the alveoli. Cases of PAP complicated with tuberculosis are much more complex and have rarely been well recorded. CASE SUMMARY: We describe a 21-year-old Han Chinese patient with suspicious lung infection associated with mild restrictive ventilatory dysfunction and diffusion reduction. High resolution computed tomography revealed a "crazy-paving" appearance and multiple pulmonary miliary nodules around the bronchi. Bronchoalveolar lavage demonstrated a small amount of periodic acid-Schiff positive proteinaceous materials. A serological test for the presence of a Mycobacterium tuberculosis antibody and an interferon-gamma release assay were both positive. The patient received a standard cours e of first-line anti-tuberculosis treatment after diagnostic bronchoalveolar lavage. To date, clinical remission has been achieved and maintained for five years. CONCLUSION: In summary, the diagnosis of PAP complicated with tuberculosis was supported by a combination of clinical manifestations, imaging, pulmonary function, laboratory examinations, bronchoalveolar lavage, etc. This case highlighted that diagnostic bronchoalveolar lavage in combination with anti-tuberculosis treatment is a safe and effective option for mild PAP patients with tuberculosis. PMID:34141807 | PMC:PMC8173423 | DOI:10.12998/wjcc.v9.i17.4400 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Schwannoma mimicking pancreatic carcinoma: A case report

paythelady.612 shared this article with you from Inoreader Schwannoma mimicking pancreatic carcinoma: A case report Μέσω pubmed: "world j clin cases"... World J Clin Cases. 2021 Jun 16;9(17):4453-4459. doi: 10.12998/wjcc.v9.i17.4453. ABSTRACT BACKGROUND: Schwannoma of the pancreas is extremely rare. We report a case of pancreatic schwannoma that was difficult to distinguish from pancreatic carcinoma before surgery. CASE SUMMARY: A 66-year-old male underwent a right-lobe hepatectomy for hepatocellular carcinoma. Post-surgical computed tomography showed a 10 mm long solid mass with ischemia, with no expansion into the main pancreatic duct. Upon magnetic resonance cholangiopancreatography, the tumor had high signal intensity in diffusion weighted images, consistent with pancreatic carcinoma. Endoscopic ultrasound (EUS) was performed to obtain more information about the tumor, and showed a 14 mm solid and hypoechoic mass in the pancreatic body. Contrast enhanced EUS revealed that the tumor showed a hyperechoic mass in the early phase, and the contrasting effect continuation was very short; findings also consistent with pancreatic carcinoma. Thus, we preoperatively diagnosed his condition as a pancreatic carcinoma and performed distal pancreatectomy with splenectomy. Microscopic examination showed that the tumor was in fact a benign schwannoma. Histology showed a proliferation of spindle-shaped cell in a vague fascicular and haphazard pattern, with palisading arrangement. CONCLUSION: Schwannoma of the pancreas is very rare, however, clinicians should consider schwannoma as the differential diagnosis for pancreatic tumors. PMID:34141813 | PMC:PMC8173407 | DOI:10.12998/wjcc.v9.i17.4453 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.