Monday, November 1, 2021

The effectiveness of alprostadil in treating coronary microcirculation dysfunction following ST-segment elevation myocardial infarction in a pig model

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Exp Ther Med. 2021 Dec;22(6):1449. doi: 10.3892/etm.2021.10884. Epub 2021 Oct 14.

ABSTRACT

Though alprostadil has been reported to improve the impaired microcirculation of patients with pulmonary arterial hypertension, its effectiveness as a treatment for coronary microvasculature dysfunction (CMD) following ST-segment elevation myocardial infarction (STEMI) is unknown. A total of 18 miniature pigs with CMD following STEMI were randomized into three groups that received an intracoronary injection of 5 ml of normal saline, 2 mg of nicorandil or 10 µg of alprostadil immediately after measurement of the index of microcirculatory resistance (IMR) and then an intravenous drip containing 5 ml of normal saline, 2 mg of nicorandil or 10 µg of alprostadil once a day for 6 days. The IMR, cardiac function using ultrasound, infarct areas and heparanase levels in infarct areas were measured and compared between the three groups. The IMR decreased markedly 10 min after alprostadil or nicorandil intracoronary injection (both P<0.05) but not following saline injection (P>0.05). After 7 days, the IMR was substantially lower in the alprostadil and nicorandil groups compared with the saline group (both P<0.05) and the ejection fraction was considerably higher in the alprostadil and nicorandil groups compared with the saline group (both P<0.05). Differences in infarct areas and the relative heparanase expression levels among the 3 groups were similar to the differences in the ejection fraction. No significant differences in the above assessment indexes were identified in the alprostadil and nicorandil groups. Alprostadil infusion improved coronary microcirculation function, reduced the infarct area and limited left ventricular dilatation in a pig coronary microvasculature dysfunction model following STEMI.

PMID:34721691 | PMC:PMC8549090 | DOI:10.3892/etm.2021.10884

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Dynamic observation of 5-fluorouracil-induced myocardial injury and mitochondrial autophagy in aging rats

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Exp Ther Med. 2021 Dec;22(6):1451. doi: 10.3892/etm.2021.10886. Epub 2021 Oct 14.

ABSTRACT

Patients treated with 5-fluorouracil (5-FU) can develop rare but potentially severe cardiac effects, including cardiomyopathy, angina pectoris, heart failure and cardiogenic shock. The specific pathologies and underlying mechanisms are yet to be fully understood. The results of previous studies have indicated that mitochondrial autophagy is widely detected in many angiocardiopathies. In the present study, the dynamic changes in the homeostasis of mitochondrial injury and autophagy were observed in rats treated with 5-FU for different durations. A corresponding control group and a 5-FU model group were established in groups of Sprague-Dawley rats aged 2 and 18 months, and the myocardial enzyme levels were determined at different time points. At 2 weeks post-model establishment, cardiac ultrasound and myocardial histological staining were performed , cardiomyocyte apoptosis and myocardial mitochondrial function were assessed, and mitochondrial ultrastructure was examined. In addition, the expression levels of autophagy-related proteins were evaluated in the 18-month-old rats on days 7 and 14 of 5-FU administration. The experimental results demonstrated that 5-FU induced an elevation in the levels of myocardial enzymes, as well as changes in the cardiac structure and function, and that these changes were more prominent over longer drug durations. In addition, 5-FU decreased the levels of myocardial mitochondrial ATP and mitochondrial membrane potential, and aggravated myocardial fibrosis and cardiomyocyte apoptosis compared with those observed in the untreated control group, treated with the same volume of saline as 5-FU in the 5-FU group. These injuries were particularly evident in aging rats. Notably, 5-FU increased the expression levels of myocardial mitochondrial autophagy-related proteins, and electron microscopy revealed a more severe autophagic state in the model groups compared with that in the control groups. In conclusion, 5-FU induced myocardial mitochondrial damage, the degree of which was more severe in aging rats compared with that in young rats. The mitochondrial autophagy induced by 5-FU was excessive, and the degree of autophagy was aggravated with increased 5-FU administration time.

PMID:34721693 | PMC:PMC8549097 | DOI:10.3892/etm.2021.10886

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Recent advances on polaprezinc for medical use (Review)

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Exp Ther Med. 2021 Dec;22(6):1445. doi: 10.3892/etm.2021.10880. Epub 2021 Oct 14.

ABSTRACT

The present study described the chemical and biological properties of zinc complex of L-carnosine (L-CAZ; generic name, polaprezinc; chemical name, catena-(S)-[µ-[N(α)-(3-aminopropionyl) histidinato (2-) N1, N2, O: N(τ)]-zinc], molecular formula, C9H14N4O3Zn; molecular weight, 291.6404; CAS registry number, 107667-60-7). Characterized as a white or yellowish white crystalline powder, this drug is insoluble in glacial acetic acid and almost insoluble in water, methanol, ethanol and ether. It is soluble in dilute hydrochloric acid, dilute nitric acid and sodium hydroxide solution, and its melting point is 260-270˚C. Polaprezinc is an anti-ulcer drug that was jointly studied and developed by Hamari Chemicals Co., Ltd. and Zeria Pharmaceutical Co., Ltd., and was first approved in Japan in 1994. This rev iew article summarizes the research advances of polaprezinc, including the patents, preparations, synthetic routes, pharmacokinetics, pharmacological effects and application in clinical research.

PMID:34721687 | PMC:PMC8549086 | DOI:10.3892/etm.2021.10880

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Exacerbation of bronchiectasis by Pseudomonas putida complicating COVID-19 disease: A case report

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Exp Ther Med. 2021 Dec;22(6):1452. doi: 10.3892/etm.2021.10887. Epub 2021 Oct 15.

ABSTRACT

Novel coronavirus infection presents with greater severity in individuals with comorbid chronic lung diseases. Bronchiectasis is an illness characterized by permanent enlargement of the airways, presenting with chronic cough and sputum production and vulnerability to lung infections. Bronchiectasis is not a common comorbid disease in patients with COVID-19 disease and bronchiectasis exacerbation rates were decreased during the pandemic. However, COVID-19 disease is associated with worse outcomes in patients with bronchiectasis and patients with bronchiectasis are more susceptible to SARS-CoV-2 infection development. Pseudomonas putida is an opportunistic pathogen, causing infections mostly in immunocompromised hosts and is not a frequent bacterial colonizer in patients with bronchiectasis. This present study reports a rare case of exacerba tion of bronchiectasis by Pseudomonas putida complicating COVID-19 disease in an immunocompetent 70-year-old woman. Clinicians should be aware that SARS-CoV-2 infection is probably a precipitating factor of bronchiectasis exacerbation while bronchiectasis is a risk factor for greater severity of SARS-CoV-2 infection.

PMID:34721694 | PMC:PMC8549101 | DOI:10.389 2/etm.2021.10887

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lncRNA RP11-531A24.3 inhibits the migration and proliferation of vascular smooth muscle cells by downregulating ANXA2 expression

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Exp Ther Med. 2021 Dec;22(6):1439. doi: 10.3892/etm.2021.10874. Epub 2021 Oct 12.

ABSTRACT

A complete understanding of the behavioral influence and phenotypic transition of vascular smooth muscle cells, as well as the effects of the characteristics of these cells on the physiological and pathological processes of atherosclerosis, is crucial if new therapeutic targets for atherosclerosis are to be identified. In the present study, the long non-coding RNA RP11-531A24.3 was identified to be expressed at low levels in plaque tissues through screening a microarray for differentially expressed genes. The functional experimental results suggested that RP11-531A24.3 reduced the viability and inhibited the migration of human aortic vascular smooth muscle cells (HA-VSMCs). RNA antisense purification-mass spectrometry was used to identify the RNA-binding proteins (RBPs) for RP11-531A24.3. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that the pathway with the highest degree of association with RP11-531A24.3 RBPs was related to cell migration. The reduced migration and viability mediated by RP11-531A24.3 overexpression was more significantly suppressed after annexin 2 (ANXA2) depletion in RP11-531A24.3-overexpressing HA-VSMCs. Culture of HA-VSMCs under hypoxic conditions (1% O2) reduced the expression of RP11-531A24.3, and enhanced the protein expression of ANXA2 and HIF-1α, while knockdown of ANXA2 downregulated the protein expression of HIF-1α. These results suggested that RP11-531A24.3 regulated the proliferation and migration of HA-VSMCs through ANXA2 expression, and hypoxia may be an external factor in the regulation of RP11-531A24.3 and its downstream targets.

PMID:34721681 | PMC:PMC8549105 | DOI:10.3892/etm.2021.10874

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Nutritional outcomes in patients undergoing transoral robotic surgery for head and neck cancers compared to conventional open surgery. A systematic review

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Abstract

This systematic review examined nutritional outcomes in patients undergoing transoral robotic surgery (TORS), compared to open surgery (OS) for head and neck cancer. PUBMED, CINAHL, and Web of Science were systematically reviewed. Target nutritional outcomes included: weight, nutritional status, use of enteral feeding, swallowing function/ability, and time to oral diet. Risk of bias was assessed using the risk of bias in non-randomized studies tool, and certainty of evidence was assessed using grading of recommendations, assessment, development, and evaluation (GRADE). Eight studies were included (total n = 608). Compared to OS, TORS probably reduces short- and long-term enteral feeding use or duration (GRADE "moderate" certainty), may reduce time to full swallow ability (GRADE "low" certainty), but it remains uncertain whether TORS reduces long-term patient reported swallowing function or time to oral feeding (GRADE "very-low" certainty). No studies e xamined nutritional status or weight. There is limited body of evidence examining nutrition outcomes following TORS. Further studies are warranted, which may improve the certainty of evidence and assist in determining the optimal nutrition care for these patients.

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An autophagy-related lncRNA prognostic risk model for thyroid cancer

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Eur Arch Otorhinolaryngol. 2021 Nov 1. doi: 10.1007/s00405-021-07134-4. Online ahead of print.

ABSTRACT

PURPOSE: Thyroid cancer (TC) is the most common malignancy of the endocrine system and its incidence is gradually rising. Research has demonstrated a close link between autophagy and thyroid cancer. We constructed a prognostic model of autophagy-related long non-coding RNA (lncRNA) in thyroid cancer and explored its prognostic value.

METHODS: The data used in this study were all obtained from The Cancer Genome Atlas (TCGA) database and the Human Autophagy Database (HADb). We construct a co-expression network by autophagy-related genes and lncRNA to obtain autophagy-related lncRNAs. After univariate Cox regression analysis and multivariate Cox regression analysis, autophagy-related lncRNAs significantly associated with prognosis were identified. Based on the risk score of lncRNA, thyroid cancer patients are divided into high-ris k group and low-risk group.

RESULTS: A total of 14,142 lncRNAs and 212 autophagy-related genes (ATGs) were obtained from the TCGA database and the HADb, respectively. We performed lncRNA-ATGs correlation analysis and finally obtained 1,166 autophagy-associated lncRNAs. Subsequently, we conducted univariate Cox regression analysis and multivariate Cox regression analysis, nine autophagy-related lncRNAs (AC092279.1, AC096677.1, DOCK9-DT, LINC02454, AL136366.1, AC008063.1, AC004918.3, LINC02471 and AL162231.2) significantly associated with prognosis were identified. Based on these autophagy-related lncRNAs, a risk model was constructed. The area under the curve (AUC) of the risk score was 0.905, proving that the accuracy of risk signature was superior. In addition, multiple regression analysis showed that risk score was a significant independent prognostic risk factor for thyroid cancer.

CONCLUSION: In this study, nine autophagy-related lncRNAs in thyroid cancer were establ ished to predict the prognosis of thyroid cancer patients.

PMID:34724113 | DOI:10.1007/s00405-021-07134-4

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