Αρχειοθήκη ιστολογίου

Κυριακή 3 Οκτωβρίου 2021

Conjunctivoductivo‐Dacryocystorhinostomy: A Novel Surgery for Intractable Canalicular Obstruction

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LINC00963 silencing inhibits the proliferation and migration of high glucose-induced retinal endothelial cells via targeting miR-27b

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Exp Ther Med. 2021 Nov;22(5):1274. doi: 10.3892/etm.2021.10709. Epub 2021 Sep 8.

ABSTRACT

The association between long intergenic non-protein-coding RNA 963 (LINC00963) and diabetes has not been fully elucidated. Therefore, the present study aimed to investigate the effect of the long non-coding RNA LINC00963 on diabetic retinopathy (DR), in order to provide a new therapeutic target for this condition. Human retinal capillary endothelial cells (HRECs) were induced with high concentrations of glucose to establish a DR model. The expression levels of LINC00963, cell viability, the protein expression levels of proliferating cell nuclear antigen (PCNA) and Ki67, and the migratory capacity of HRECs were determined using reverse transcription-quantitative PCR (RT-qPCR), Cell Counting Kit-8 assay, western blot analysis, and wound healing and Transwell assays, respectively. Furthermore, the Encyclopedia of RNA Interactomes database was used to predict the binding targets of LINC00963, and luciferase reporter assay was used to verify the direct binding of microRNA (miR)-27b to LINC00963. RT-qPCR was also utilized to measure the expression levels of miR-27b, PCNA and Ki67. The results demonstrated that LINC00963 silencing inhibited glucose-induced HREC proliferation and migration, and downregulated PCNA and Ki67 expression. Following transfection with miR-27b inhibitor, cell proliferation and migration were notably enhanced, and the protein expression levels of PCNA and Ki67 were increased. Taken together, the results of the present study suggested that the LINC00963/miR-27b axis may regulate the proliferation and migration of glucose-induced HRECs. Therefore, LINC00963 may be considered as a potential therapeutic target for DR.

PMID:34594411 | PMC:PMC8456487 | DOI:10.3892/etm.2021.10709

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Se alleviates homocysteine-induced fibrosis in cardiac fibroblasts via downregulation of lncRNA MEG3

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Exp Ther Med. 2021 Nov;22(5):1269. doi: 10.3892/etm.2021.10704. Epub 2021 Sep 7.

ABSTRACT

Selenium (Se) is considered to have antioxidant properties, which are beneficial for heart condition. Hyperhomocysteinemia (HHCY) has been suggested to potentially lead to heart failure and is characterized by cardiac fibrosis; however, investigation on the role of Se and HHCY in cardiac fibrosis is rare. Since previous studies demonstrated the important role of the long non-coding RNA maternally expressed 3 (MEG3) in some heart diseases, the present study aimed to determine how Se and MEG3 might exert regulatory effects on HCY-induced fibrosis in cardiac fibroblasts (CFs). Mouse CFs were isolated and treated with HCY and Se. The expression of α-smooth muscle actin (α-SMA), collagen I and III was detected by western blotting to reflect CF fibrosis. Reverse transcription-quantitative PCR was performed to determine the expression levels of MEG3. I nflammation and oxidative stress responses were analyzed by measuring TNF-α, IL-1β (ELISA) and reactive oxygen species levels (using a commercial kit), respectively. Cell Counting Kit-8 was used to evaluate CF proliferation. Total and phosphorylated (p) expression of janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) was evaluated by western blotting. CFs were transfected with adenovirus expressing MEG3 short-hairpin RNA to knock down MEG3 expression. Se treatment downregulated the expression level of MEG3 in HCY-stimulated CFs, whilst inhibiting the inflammatory and oxidative stress response. Furthermore, Se inhibited the increased proliferation of CFs following HCY treatment. In addition, MEG3-knockdown in CFs could improve fibrosis caused by HCY. Furthermore, the ratios of p-JAK2/JAK2 and p-STAT3/STAT3 were decreased following treatment with Se or MEG3 silencing. Taken together, the findings from the present study suggested that Se may alleviat e cardiac fibrosis by downregulating the expression of MEG3 and reducing the inflammatory and oxidative stress response in CFs. This suggests that Se may be a potential therapeutic option for treating cardiac fibrosis in the future.

PMID:34594406 | PMC:PMC8456485 | DOI:10.3892/etm.2021.10704

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Novel function of fluvastatin in attenuating oxidized low-density lipoprotein-induced endothelial cell ferroptosis in a glutathione peroxidase4- and cystine-glutamate antiporter-dependent manner

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Exp Ther Med. 2021 Nov;22(5):1275. doi: 10.3892/etm.2021.10710. Epub 2021 Sep 8.

ABSTRACT

Oxidized low-density lipoprotein (ox-LDL) induces endothelial cell apoptosis and dysfunction. Statins are drugs that are clinically used to lower serum cholesterol levels, and they have been shown to exert vascular protective effects. In the present study, human umbilical vein endothelial cells were transfected with scramble control siRNA or siRNA specific for glutathione peroxidase (GPx)4 or cystine-glutamate antiporter (xCT). MTT, Matrigel and Transwell assays were used to evaluate cell proliferation, tube formation and migration, respectively. The levels of TNF-α, IL-α, 4-hydroxynonenal, GPx4 and xCT expression were detected by western blot analysis. It was demonstrated that ox-LDL promoted cytokine production and reduced the proliferation, migration and angiogenesis of endothelial cells. It was also observed that ox-LDL decreased GPx4 and xC T expression and induced ferroptosis. Furthermore, the inhibition of ferroptosis by deferoxamine mesylate attenuated ox-LDL-induced endothelial cell dysfunction and restored ox-LDL-decreased GPx4 and xCT expression. Consistent with these results, GPx4 and xCT knockdown by siRNA transfection aggravated ox-LDL-induced endothelial cell dysfunction and inhibition of proliferation. To the best of our knowledge, the present study was the first to discover that fluvastatin may protect endothelial cells from ox-LDL-induced ferroptosis and dysfunction. Furthermore, knockdown of GPx4 and xCT expression blunted the protective effects of fluvastatin on ox-LDL-treated endothelial cells. These data indicated a novel function of fluvastatin in the protection of endothelial cells from ox-LDL-induced ferroptosis, the mechanism of which involves the regulation of GPx4 and xCT.

PMID:34594412 | PMC:PMC8456483 | DOI:10.3892/etm.2021.10710

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Vasculitis associated with the use of an intrauterine device: A case report

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Exp Ther Med. 2021 Nov;22(5):1277. doi: 10.3892/etm.2021.10712. Epub 2021 Sep 8.

ABSTRACT

Retinal vasculitis is a complication associated with a local condition or it can be a retinal expression of a systemic inflammatory disorder, which initially may go unnoticed. Drug-associated vasculitis is frequently difficult to identify, because many patients follow treatments with more than one drug and the route of administration varies. A 35-year-old female patient presented with sudden hearing loss, headache and blurred vision that had started two weeks earlier and had become progressively worse. Ophthalmological examination revealed anterior uveitis, bilateral optic disc swelling and retinal vasculitis. The orbito-cerebral MRI, the CT scan and the serological tests were within normal limits. Unable to identify the cause of the retinal vasculitis, the patient's medical history was reviewed. The patient had recently had a gynecological proced ure, where a 13.5 mg levonorgestrel intrauterine contraceptive device was implanted. After the device was removed and methylprednisolone treatment started, the patient presented a visible remission of the symptoms and signs. To the best of our knowledge, there is no case of retinal disease and optic disc edema associated with auditory problems caused by an intrauterine device. A proper examination, correlated with a very thorough medical history, could identify rare diseases and associations, in order to provide adequate medical care.

PMID:34594414 | PMC:PMC8456497 | DOI:10.3892/etm.2021.10712

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Association between obesity and iron deficiency (Review)

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Exp Ther Med. 2021 Nov;22(5):1268. doi: 10.3892/etm.2021.10703. Epub 2021 Sep 7.

ABSTRACT

Obesity is a risk factor for several comorbidities and complications, including iron deficiency anemia. Iron deficiency anemia is a serious global public health problem, with a worldwide prevalence. The high prevalence of obesity in combination with iron deficiency incidence observed in different age and sex categories suggests an association between obesity and iron status. Obesity may disrupt iron homeostasis, resulting in iron deficiency anemia. The association between obesity and iron deficiency may be due to increased hepcidin levels mediated by chronic inflammation. Hepcidin is a small peptide hormone that functions as a negative regulator of intestinal iron absorption. Significant body weight loss in overweight and obese individuals decreases chronic inflammation and serum hepcidin levels, resulting in improved iron status due to increased iron absorption. However, further randomized controlled trials are required to confirm this effect.

PMID:34594405 | PMC:PMC8456489 | DOI:10.3892/etm.2021.10703

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miR-122-5p downregulation attenuates lipopolysaccharide-induced acute lung injury by targeting IL1RN

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Exp Ther Med. 2021 Nov;22(5):1278. doi: 10.3892/etm.2021.10713. Epub 2021 Sep 8.

ABSTRACT

MicroRNAs (miRs) and inflammatory cytokines can induce acute lung injury (ALI), which can develop into acute respiratory distress syndrome in severe cases. Previous research has revealed that miR-122-5p participates in the development of ALI, and that its expression is positively associated with ALI. However, the mechanism by which miR-122-5p contributes to ALI remains to be determined. In the current study, TargetScan and dual luciferase reporter gene assays were used to confirm that IL-1 receptor antagonist (IL1RN) was a target of miR-122-5p. Subsequently, by referring to previous literature, a lipopolysaccharide (LPS)-induced ALI cell model was established. A549 cells were transfected with mimic control or miR-122-5p mimics for 24 h, and 10 µg LPS was used to treat the transfected cells for 12 h. The results revealed that miR-122-5p mimics dec reased cell viability and promoted apoptosis. Lactate dehydrogenase (LDH) release assays indicated that miR-122-5p mimics increased LDH release. ELISA demonstrated that miR-122-5p mimics promoted TNF-α, IL-1β and IL-6 expression levels. A549 cells were transfected with inhibitor control, miR-122-5p inhibitor, miR-122-5p inhibitor + control-small interfering (si)RNA or miR-122-5p inhibitor + IL1RN-siRNA for 24 h, after which the cells were treated with 10 µg LPS for 12 h. The results revealed that the effects of the miR-122-5p inhibitor were the opposite of those of the miR-122-5p mimic. All the effects of miR-122-5p inhibitor on LPS-treated A549 cells were significantly reversed by IL1RN-siRNA. Overall, the results highlighted miR-122-5p as a potential novel target for the treatment of ALI.

PMID:34594415 | PMC:PMC8456493 | DOI:10.3892/etm.2021.10713

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Role of circular RNAs in osteoarthritis (Review)

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Exp Ther Med. 2021 Nov;22(5):1279. doi: 10.3892/etm.2021.10714. Epub 2021 Sep 9.

ABSTRACT

Osteoarthritis (OA) is a chronic bone and joint disease characterized by articular cartilage degeneration and joint inflammation. OA is the most common form of arthritis, and the major clinical manifestations of OA are chronic pain and joint activity disorder, which severely affect patients' quality of life. Circular RNA (circRNA) is a type of non-coding RNA that is ubiquitous in eukaryotic cells. Unlike standard linear RNAs, they form a covalently closed continuous loop without 5' or 3' polarity. They are usually considered as byproducts of mis-splicing or mRNA processing. CircRNAs have been detected and identified in numerous species. Various studies have confirmed that certain circRNAs are differentially expressed in OA cartilage and are closely associated with a variety of pathological processes of OA, including extracellular matrix degradatio n, inflammation and apoptosis. The present study reviewed the latest research on circRNAs in the pathogenesis of OA, providing a novel direction for the prevention, diagnosis and treatment of OA.

PMID:34594416 | PMC:PMC8456490 | DOI:10.3892/etm.2021.10714

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Emerging roles of growth differentiation factor-15 in brain disorders (Review)

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Exp Ther Med. 2021 Nov;22(5):1270. doi: 10.3892/etm.2021.10705. Epub 2021 Sep 7.

ABSTRACT

Brain disorders, such as Alzheimer's and Parkinson's disease and cerebral stroke, are an important contributor to mortality and disability worldwide, where their pathogenesis is currently a topic of intense research. The mechanisms underlying the development of brain disorders are complex and vary widely, including aberrant protein aggregation, ischemic cell necrosis and neuronal dysfunction. Previous studies have found that the expression and function of growth differentiation factor-15 (GDF15) is closely associated with the incidence of brain disorders. GDF15 is a member of the TGFβ superfamily, which is a dimer-structured stress-response protein. The expression of GDF15 is regulated by a number of proteins upstream, including p53, early growth response-1, non-coding RNAs and hormones. In particular, GDF15 has been reported to serve an importan t role in regulating angiogenesis, apoptosis, lipid metabolism and inflammation. For example, GDF15 can promote angiogenesis by promoting the proliferation of human umbilical vein endothelial cells, apoptosis of prostate cancer cells and fat metabolism in fasted mice, and GDF15 can decrease the inflammatory response of lipopolysaccharide-treated mice. The present article reviews the structure and biosynthesis of GDF15, in addition to the possible roles of GDF15 in Alzheimer's disease, cerebral stroke and Parkinson's disease. The purpose of the present review is to summarize the mechanism underlying the role of GDF15 in various brain disorders, which hopes to provide evidence and guide the prevention and treatment of these debilitating conditions.

PMID:34594407 | PMC:PMC8456456 | DOI:10.3892/etm.2021.10705

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HPV vaccine for men: Where to? (Review)

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Exp Ther Med. 2021 Nov;22(5):1266. doi: 10.3892/etm.2021.10701. Epub 2021 Sep 7.

ABSTRACT

Human papillomavirus (HPV) is one of the most widespread human pathogens. For a long time, it was treated as an opportunistic infection, but it is in actuality one of the most dangerous carcinogens. It is responsible for numerous malignancies: Cervical, penile, oropharyngeal, vaginal, vulvar and some anal neoplasia. The need for a long-term solution was evident and thus HPV vaccines were proven to be a viable solution. Women and men who have sex with men, and young men are included in the vaccination template. A thorough review using PubMed and other databases that included articles on vaccine templates and targeted male patients was carried out. After review of all of the studies conducted on this subject, there is a clear benefit for HPV vaccination for men. Yet, even with the introduction of a national vaccine program for HPV for women and girl s in most developed countries, regarding the male vaccine program, few countries have established a national program. Still, a gender-neutral vaccine remains a controversial issue. It is important to monitor the impact of HPV vaccine in men and the benefits that occur, to inform and spread the results in order to implement this vaccine program worldwide. Any monitoring plan regarding the HPV vaccination must include HPV prevalence, anogenital warts, and anal cancer. The largest impact regarding the range of this type of vaccine is the surveillance of the specific targeted population. HPV vaccine is a very efficient immunization method. Women are obviously the first target, but there are still many contradictions regarding men. Most of the reasons reside in the cost-efficiency aspect, but there is still great debate regarding the most efficient vaccine in the male population.

PMID:34594403 | PMC:PMC8456458 | DOI:10.3892/etm.2021.10701

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Association Between Neonates With Laryngomalacia and Neonatal Abstinence Syndrome

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Ann Otol Rhinol Laryngol. 2021 Oct 1:34894211048278. doi: 10.1177/00034894211048278. Online ahead of print.

ABSTRACT

OBJECTIVE: Laryngomalacia (LM) is the most common congenital anomaly of the larynx. The cause of LM is still largely unknown, but a neurological mechanism has gained the most acceptance. There have not been any studies examining the prevalence of LM in infants with Neonatal Abstinence Syndrome (NAS). The aim of our study is to determine if infants with NAS are more likely to be diagnosed with LM.

METHODS: This study was a population-based inpatient registry analysis. We examined nationwide neonatal discharges in 2016 using the Kids' Inpatient Database (KID). Only patients listed as neonates were included. The International Classification of Diseases, 10th revision, Clinical Modification (ICD-10-CM) codes for neonatal withdrawal symptoms from maternal use of drugs of addiction (P96.1) and diagnoses denoting LM were used. To quantify associations between the LM and NAS groups, prevalence rates and odds ratios (ORs) were used.

RESULTS: There were 3 970 065 weighted neonatal discharges in the 2016 KID. Among patients included in our dataset, 0.809% (32 128) had NAS and 0.075% (2974) had LM. There was an increased odds ratio for neonates with NAS and LM (OR of 2.85, 95% CI = 2.24-3.63) compared to infants without NAS. Multiple logistic regression accounting for possible confounders produced an adjusted OR of 1.68 (95% CI = 1.29-2. 19).

CONCLUSION: Our study found an association between NAS and LM. This suggests that prenatal exposure to opioids or possibly the sequelae of withdrawal symptoms may be risk factors for the development of LM.

PMID:34595938 | DOI:10.1177/00034894211048278

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