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Δευτέρα 1 Νοεμβρίου 2021

Identification and functional annotation of differentially expressed long noncoding RNAs in retinoblastoma

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Exp Ther Med. 2021 Dec;22(6):1447. doi: 10.3892/etm.2021.10882. Epub 2021 Oct 14.

ABSTRACT

Retinoblastoma (RB), the most common intraocular malignancy, typically occurs in pediatric patients under the age of 6 years. The present study aimed to explore the long noncoding RNA (lncRNA) expression profile in RB and identify novel lncRNA biomarkers to facilitate the investigation of molecular mechanisms of RB and improve clinical therapy. Raw microarray data for the comparison of gene expression between three RB and three adjacent normal tissue samples were downloaded from Gene Expression Omnibus (dataset no. GSE111168). After identification of differentially expressed lncRNAs (DELs) and differentially expressed mRNAs (DEMs) in RB, functional enrichment analyses and a DEL-DEM weighted correlation network analysis were performed. A total of 3,915 DELs (1,774 upregulated and 2,141 downregulated) and 3,715 DEMs (1,492 upregulated and 2,223 dow nregulated) were identified in RB. The DEL-targeted DEMs were highly enriched by genes involved in hexose transport, muscle tissue morphogenesis, the stereocilium membrane, endothelin B receptor binding and γ-filamin/ABP-L, α-actinin and telethonin binding protein of the Z-disc binding. Furthermore, associations of the DELs and DEMs with several pathways were determined, including PI3K/AKT, Hippo and cancer signaling, as well as extracellular matrix-receptor interaction pathways. Coexpression network analysis revealed that the top three DELs, lnc-DAZ1-161, lnc-HDAC7-21 and lnc-OR52A1-55, formed coexpression modules with 181, 156 and 210 DEMs, respectively. In addition, the top three DEMs, namely EIF1AY, GSTM1 and NLRP11, formed coexpression modules with 33, 50 and 41 DELs, respectively. Validation using reverse transcription-quantitative PCR indicated that the expression of representative lncRNAs (lnc-DAZ1-161 and lnc-HDAC7-21) in RB cells in vitro was consistent with that in RB tissues in the database, while the expression of lnc-OR52A1-55 was not consistent with the database. These results suggested that the aberrant lncRNA expression profile in RB is related to the differential regulation of numerous physiological and pathological processes. The lncRNA and mRNA profiles in RB identified may provide novel targets for the investigation of its molecular mechanisms and thus lead to improvements in clinical therapy for RB.

PMID:34721689 | PMC:PMC 8549103 | DOI:10.3892/etm.2021.10882

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Repeated exposure to sevoflurane in neonatal rats impairs cognition in adulthood via the PKA-CREB-BDNF signaling pathway

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Exp Ther Med. 2021 Dec;22(6):1442. doi: 10.3892/etm.2021.10877. Epub 2021 Oct 13.

ABSTRACT

Sevoflurane (Sev) anesthesia is widely used in pediatrics due to its low blood-gas partition coefficient and lack of pungency. However, Sev treatment may lead to cognitive dysfunction in later life. The current study administered Sev to neonatal rats to investigate the effects of Sev treatment on cognitive performance in adulthood. In total, 6-day-old rats received 3% Sev for 2 h daily for 3 consecutive days. The cognitive function of rats in adulthood was evaluated in 56-day-old rats by Morris water maze test. The hippocampal neuron morphology was observed by Nissl staining. Hippocampal brain-derived neurotrophic factor (BDNF) levels were measured by ELISA. The protein expression of protein kinase A (PKA), cAMP response element binding protein (CREB), phosphorylated-CREB (p-CREB) and BDNF in hippocampus were assessed by western blotting. The wat er maze results demonstrated that neonatal treatment with Sev resulted in a significant impairment of cognition in 56-day-old adult rats. Behavioral analysis revealed that Sev treatment increased latency to first pass the platform and decreased residence in target quadrants and across platform frequency compared with the control group in Morris water maze tests. Furthermore, compared with the control group, neonatal exposure to Sev reduced the number of neurons and the concentration of BDNF in the hippocampus, a brain region important for learning and memory. Additionally, Sev significantly decreased the expression of PKA, p-CREB, BDNF and the p-CREB/CREB ratio. Treatment with bucladesine, a selective PKA agonist, partially reversed the deleterious effects of Sev. In summary, the results indicated that PKA-CREB-BDNF signaling served an important role in the cognitive decline caused by neonatal exposure to Sev.

PMID:34721684 | PMC:PMC8549089 | DOI:10.3892/etm.2021.10877

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miR-663b promotes tumor cell proliferation, migration and invasion in nasopharyngeal carcinoma through targeting TUSC2

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Exp Ther Med. 2021 Dec;22(6):1448. doi: 10.3892/etm.2021.10883. Epub 2021 Oct 14.

ABSTRACT

[This retracts the article DOI: 10.3892/etm.2017.4608.].

PMID:34721690 | PMC:PMC8549096 | DOI:10.3892/etm.2021.10883

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Overactive bladder: A review and update

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Exp Ther Med. 2021 Dec;22(6):1444. doi: 10.3892/etm.2021.10879. Epub 2021 Oct 14.

ABSTRACT

Overactive bladder syndrome is a chronic, disabling condition with physical, psychological and social consequences that significantly affects the quality of life of millions of patients worldwide. The economic impact of this disorder is crucial. Overactive bladder syndrome is a little-known condition, with different manifestations from patient to patient, which causes a great deal of frustration to the medical staff involved. The patient requires a clear explanation and the full support of the attending physician. It is extremely important to establish a correct diagnosis and an effective individualized treatment. The collaboration and understanding of these patients are extremely important aspects. Improving the quality of life in these patients is the main purpose in managing this condition. There are several treatment modalities that may be us ed progressively, with favorable albeit inconsistent results. This condition remains extremely challenging for specialists and, unfortunately, always one of maximum interest.

PMID:34721686 | PMC:PMC8549091 | DOI:10.3892/etm.2021.10879

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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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