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Δευτέρα 1 Νοεμβρίου 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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Emergence of bla TEM, bla CTX-M, bla SHV and bla OXA genes in multidrug-resistant Enterobacteriaceae and Acinetobacter baumannii in Saudi Arabia

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Exp Ther Med. 2021 Dec;22(6):1450. doi: 10.3892/etm.2021.10885. Epub 2021 Oct 14.

ABSTRACT

Multidrug-resistant (MDR) patterns due to extended-spectrum β-lactamase (ESBL) production in pathogenic bacteria are now becoming prevalent in hospitals worldwide, posing a public health challenge. The aim of the present study was to determine the antibiotic susceptibility patterns and distribution of the bla TEM, bla CTX-M, bla SHV and bla OXA ESBL resistance genes in MDREnterobacteriaceae and Acinetobacter baumannii (A. baumannii). A cross-sectional study was conducted between September 2017 and August 2018 in the King Abdullah Hospital (Bisha, Saudi Arabia). Bacterial isolates were collected from the clinical samples of patients; these were identified and screened for ESBL production and their antibiotic susceptibility was examined using standard microbiolog y methods. Multiplex-PCR runs were performed to identify genes encoding ESBL producers. DNA sequencing analysis was used to identify the specific gene variants. Of the 274 isolates, 173 (63.1%) exhibited MDR patterns to different antibiotics. A. baumannii revealed the highest resistance rates for cefuroxime (100%), gentamicin (88%) and amikacin (86%). Klebsiella pneumoniae (K. pneumoniae) isolates had the highest resistance rates for cefuroxime (98%), aztreonam and trimethoprim/sulfamethoxazole (87% for each). Escherichia coli (E. coli) exhibited high resistance rates for trimethoprim/sulfamethoxazole (92%) and cefuroxime (87%). Of the 173 MDR isolates, 78 (45.1%) exhibited ESBL production. Of these, 88.9% (72/78) carried ESBL genes. The most prevalent gene-encoding isolates were bla TEM (84.7%), followed by bla CTX-M (33.3%), bla SHV (2.7%) and bla OXA-1 (1.4%). A single bla TEM gene was predominantly produced by K. pneumoniae (60.7%), A. baumannii (78.9%) and Proteus mirabilis (80%), whereas bla CTX-M was harbored by E. coli (33.3%). The co-existence of two different genes in a single bacterium was revealed in 22.2% of isolates, commonly between bla TEM and bla CTX-M (19.4%). Sequencing analysis revealed that bla CTX-M-15 and bla TEM-1 were predominant variants of the bla CTX-M and bla TEM genes, respectively. The present study revealed a diversity of ESBL genes in Gram-negative bacterial isolates, with bla TEM being the most prevalent type. The emergence of various ESBL genes with several co-existing genotypes is alarming, rendering extensive surveillance studies necessary to understand the transmission and epidemiology of such resistant gene-carrying isolates.

PMID:34721692 | PMC:PMC8549092 | DOI:10.3892/etm.2021.10885

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Semaphorin 7A knockdown improves injury and prevents endothelial-to-mesenchymal transition in ox-LDL-induced HUVECs by regulating β1 integrin expression

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Exp Ther Med. 2021 Dec;22(6):1441. doi: 10.3892/etm.2021.10876. Epub 2021 Oct 13.

ABSTRACT

Atherosclerosis is the most common cause of cardiovascular disease and is accompanied by high mortality rates and a poor prognosis. Semaphorin 7A (Sema7A) and its receptor β1 integrin have been reported to participate in the development of atherosclerosis. However, the role of Sema7A and β1 integrin in endothelial cell injury and endothelial-to-mesenchymal transition (EMT) in atherosclerosis remains undetermined, to the best of our knowledge. The mRNA and protein expression levels of Sema7A and β1 integrin in HUVECs were analyzed using reverse transcription-quantitative PCR (RT-qPCR) and western blot analyses, respectively. HUVECs were induced with 50 µg/ml oxidized low-density lipoprotein (ox-LDL) to establish an atherosclerosis cell model. Cell viability was measured using Cell Counting Kit-8 assay and the production of IL-1β, IL-6 and C-C motif chemokine ligand 2 was determined using ELISA. The expression levels of cell adhesion factors, intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 were analyzed using RT-qPCR and western blot analyses. Cell apoptosis was detected using flow cytometry and western blotting. The levels of EMT-related markers were evaluated using RT-qPCR, western blotting and immunofluorescence staining. The results of the present study revealed that the expression levels of Sema7A and β1 integrin were significantly upregulated in ox-LDL-treated HUVECs. Treatment with ox-LDL significantly decreased cell viability, and increased the levels of inflammatory and adhesion factors, the cell apoptotic rate and the expression levels of EMT-related proteins. Knockdown of Sema7A reversed the ox-LDL-induced inflammatory responses and EMT, while the overexpression of β1 integrin reversed the Sema7A-mediated inhibitory effects on ox-LDL-treated HUVECs. In conclusion, the findings of the present study indicated that Sema7A and β1 integrin may play significant roles in atherosclerosis by mediating endothelial cell injury and EMT progression.

PMID:34721683 | PMC:PMC8549106 | DOI:10.3892/etm.2021.10876

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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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Protective effects of flavonoids from the leaves of Carya cathayensis Sarg. against H2O2-induced oxidative damage and apoptosis in vitro

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Exp Ther Med. 2021 Dec;22(6):1443. doi: 10.3892/etm.2021.10878. Epub 2021 Oct 13.

ABSTRACT

Hydrogen peroxide (H2O2) can induce apoptosis by releasing reactive oxygen species (ROS) and reactive nitrogen species, which cause mitochondrial damage. The present study aimed to investigate the protective effects of flavonoids from the leaves of Carya cathayensis Sarg. against H2O2-induced oxidative damage and apoptosis in vitro. The bioactivity of total flavonoids (TFs) and five monomeric flavonoids [cardamonin (Car), pinostrobin chalcone, wogonin, chrysin and pinocembrin] from the leaves of Carya cathayensis Sarg. (LCCS) were tested to prevent oxidative damage to rat aortic endothelial cells (RAECs) induced by H2O2. Oxidated superoxide dismutase, glutathione peroxidase, malondialdehyde, lactate dehydrogenase and ROS were analyzed to evaluate the antioxidan t activity. Gene and protein expression patterns were assessed using reverse transcription-quantitative PCR and western blotting, respectively. The results indicated that TFs and Car inhibited H2O2-induced cytotoxicity and apoptosis of RAECs. Additionally, they regulated the level of oxidase and inhibited the production of ROS. Overall, the TFs extracted from LCCS could potentially be developed as effective candidate drugs to prevent oxidative stress in the future; moreover, they could also provide a direction in investigations for preventing antioxidant activity through the ROS pathway.

PMID:34721685 | PMC:PMC8549100 | DOI:10.3892/etm.2021.10878

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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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