Τετάρτη 4 Αυγούστου 2021

Knockdown of circ_0001883 may inhibit epithelial-mesenchymal transition in laryngeal squamous cell carcinoma via the miR-125-5p/PI3K/AKT axis

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Exp Ther Med. 2021 Sep;22(3):1007. doi: 10.3892/etm.2021.10440. Epub 2021 Jul 15.

ABSTRACT

Laryngeal squamous cell carcinoma (LSCC) is a malignant tumor with increasing incidence and poor prognosis. Circular RNAs (circRNAs) are known to modulate tumorigenesis and cancer development that may function through microRNAs (miRs). The aim of the present study was to investigate the functional roles of circ_0001883 in LSCC and the underlying molecular mechanism. The expression of circ_0001883 was upregulated and measured using reverse transcription-quantitative PCR (RT-qPCR) and RNase R. miR-125b-5p expression was downregulated in LSCC tissues and cells as determined using RT-qPCR. Subsequently, knockdown of circ_0001883 inhibited LSCC cell migration, invasion and epithelial-mesenchymal transition (EMT), which were tested by wound healing assays, Transwell assays and western blotting, respectively. Bioinformatics analysis predicted that circ_ 0001883 was a sponge of miR-125b-5p, which was verified using a dual-luciferase reporter assay. Knockdown of circ_0001883 played a functional role by sponging miR-125b-5p. Additionally, circ_0001883 and miR-125b-5p influenced phosphorylation of PI3K and AKT, detected via western blotting. In an in vivo study, knockdown of circ_0001883 reduced tumor volume and weight in mice, along with enhanced miR-125b-5p and E-cadherin expression levels, and decreased N-cadherin, phosphorylated (p)-PI3K/PI3K and p-AKT/AKT ratios. In conclusion, knockdown of circ_0001883 inhibited cell migration, invasion and EMT of LSCC by sponging miR-125b-5p. This is hypothesized to be via the PI3K/AKT signaling pathway, which suggested that circ_0001883 has potential for LSCC therapy.

PMID:34345289 | PMC:PMC8311254 | DOI:10.3892/etm.2021.10440

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Orthopedic surgery in hemophilic patients with musculoskeletal disorders: A systematic review

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Exp Ther Med. 2021 Sep;22(3):995. doi: 10.3892/etm.2021.10427. Epub 2021 Jul 14.

ABSTRACT

Hemophilia is a hereditary coagulopathy caused by factor VIII (hemophilia type A) or by coagulation factor IX (hemophilia type B) dysfunction, characterized by an increased bleeding predisposition, which is either spontaneous or secondary to minimal trauma. Currently, hemophilia may also be considered an 'orthopedic' condition, due to the fact that it affects the musculoskeletal system of most hemophilic patients. In recent years, constant prophylaxis using coagulation factors has led to a significant improvement in the hemophilic patient's quality of life, by reducing both life-threatening hemorrhagic phenomena, as well as the occurrence of chronic complications. Nevertheless, progressive joint bleeding remains unavoidable in this category of patients, and the onset of chronic arthropathy with secondary motor deficiency remains the main complicat ion with an invalidating character. In such cases, orthopedic management is imperative; osteoarticular complications being managed most often with the help of conservative or surgical techniques. The purpose of this review is to provide an overview of modern orthopedic practices which are useful in the management of hemophilic patients suffering from osteoarticular disorders.

PMID:34345277 | PMC:PMC8311230 | DOI:10.3892/etm.2021.10427

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DL-3-n-butylphthalide protects H9c2 cardiomyoblasts from ischemia/reperfusion injury by regulating HSP70 expression via PI3K/AKT pathway activation

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Exp Ther Med. 2021 Sep;22(3):1008. doi: 10.3892/etm.2021.10441. Epub 2021 Jul 15.

ABSTRACT

DL-3-n-butylphthalide (NBP) is commonly used to treat ischemic strokes due to its antioxidative and anti-inflammatory effects. The present study aimed to examine the protective effects of NBP on myocardial ischemia-reperfusion injury (MIRI) by establishing a MIRI model in H9c2 cells. Cell viability assay using Cell Counting Kit-8, lactate dehydrogenase (LDH) cytotoxicity and lipid peroxidation malondialdehyde (MDA) content were assessed to detect cell activity, degree of cell injury and oxidative stress reaction. Reverse transcription-quantitative PCR was used to quantify the expression of inflammatory factors in H9c2 cells. Western blotting and immunofluorescence staining were used to detect the protein expression of PI3K/AKT and heat shock protein 70 (HSP70). The present results indicated that NBP significantly increased cell viability during i schemia-reperfusion. Moreover, NBP inhibited the release of LDH and the production of MDA. NBP treatment also significantly decreased the expression of inflammatory factors at the mRNA level. Additionally, NBP activated the PI3K/AKT pathway and upregulated the expression of HSP70 compared with cells in the MIRI model. LY294002, a PI3K inhibitor, reversed the protective effects of NBP and suppressed the expression of HSP70. The present study demonstrated that NBP protected H9c2 cells from MIRI by regulating HSP70 expression via PI3K/AKT pathway activation.

PMID:34345290 | PMC:PMC8311253 | DOI:10.3892/etm.2021.10441

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Optimization of a GF-AAS method for lead testing in blood and urine: A useful tool in acute abdominal pain management in emergency

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Exp Ther Med. 2021 Sep;22(3):985. doi: 10.3892/etm.2021.10417. Epub 2021 Jul 13.

ABSTRACT

Suspicion of lead poisoning is confirmed by its concentration in blood and protoporphyrin red blood cells. At low concentrations, lead influences the synthesis of the heme in the sense of lowering it. Acute and chronic lead intoxication is extremely polymorphic in regards to its clinical manifestations, with digestive, hematological, cardiovascular, renal hepatic and neurological features. The aim of the study was to evaluate the presence of lead in human whole blood and urine harvested before and during chelation treatment in the case of lead poisoning. An atomic absorption spectroscopic method for the analysis of lead was developed using graphite furnace atomic absorption spectrophotometer (GF-AAS), Varian Spectra AA-880 with a hollow cathode lead lamp and a deuterium lamp for background correction, coupled to a GTA-100 atomizer and a programmab le sample dispenser. Standard calibration solutions were used for the range 10-100 µg/l. The linearity range was 10.0 to 100.0 µg/l with the correlation coefficient of 0.999. We established that the method can be applied for the determination of lead in whole blood and urine, and the results obtained are useful for monitoring chelation therapy in cases of acute lead poisoning, a neglected cause of abdominal colic pain in an emergency situation.

PMID:34345267 | PMC:PMC8311247 | DOI:10.3892/etm.2021.10417

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Advances in molecular mechanisms of pelvic organ prolapse (Review)

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Exp Ther Med. 2021 Sep;22(3):1009. doi: 10.3892/etm.2021.10442. Epub 2021 Jul 15.

ABSTRACT

Pelvic organ prolapse (POP) is a common gynecological benign disease occurring in middle-aged and elderly females. Its incidence increases every year. To date, the majority of studies investigating its etiology have not evaluated the underlying molecular mechanisms, which has caused substantial difficulties in the prevention, treatment and prognosis of POP. In the present narrative review, recent research studies concerning the molecular mechanisms of POP were systematically reviewed and the advances were summarized. The association between the incidence of POP and the reduction of the extracellular matrix, activation of oxidative stress, genetic susceptibility, denervation of the pelvic floor and reduction of estrogen infiltration were explored. POP is mainly associated with damage of pelvic floor muscles and connective tissue, which are directl y caused by pregnancy and vaginal delivery. The majority of the molecular and genetic mutations associated with POP involve specific components of connective tissue synthesis and degradation. It is likely that macroscopic parameters, such as anatomy, lifestyle and reproductive factors, interact with microscopic parameters, such as physiology and genetics in the female pelvic floor, leading to POP. Additional research studies investigating the molecular mechanisms of POP should be performed, since they may aid public health strategies. In the present narrative review, a summary of these molecular mechanisms underlying the development of POP is provided. This included the relevant proteins and genes involved. On this basis, countermeasures were proposed.

PMID:34345291 | PMC:PMC8311251 | DOI:10.3892/etm.2021.10442

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Efficacy of supplementation with methylcobalamin and cyancobalamin in maintaining the level of serum holotranscobalamin in a group of plant-based diet (vegan) adults

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Exp Ther Med. 2021 Sep;22(3):993. doi: 10.3892/etm.2021.10425. Epub 2021 Jul 14.

ABSTRACT

Plant-based nutrition has become extremely popular in the contemporary era. Its positive effects are sustained by many studies, but one of its risks is that it is almost completely devoid of vitamin B12. In the present study, we analyzed the effects of two types of vitamin B12 supplements, cyancobalamin and methylcobalamin on the level of active serum vitamin (holotranscobalamin) in a group of Romanian individuals (n=42) following a (vegan) plant-based diet. The results revealed that cyancobalamin gives better results in maintaining B12, as quantified by the holotranscobalamin value (median=150 pcg/l) when compared with methylcobalamin (median=78.5 pcg/l). The frequency of administration, regardless of the quantity in one dose, is another important factor in maintaining the holotranscobalamin level within suitable limits. More frequent intakes giv e more optimal results. Vegans trying to supplement with alternative products (algae, kombucha, other fermented products), had the lowest levels of holotranscobalamin, always bellow the recommended level of 35 pcg/l (median=29 pcg/l). Vegans must be educated on B12 supplementation, about the pharmaceutical forms on the market and their performances and on choosing the optimal plan in order to avoid the onset of B12 deficiency.

PMID:34345275 | PMC:PMC8311243 | DOI:10.3892/etm.2021.10425

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Current advances in metabolomic studies on non-motor psychiatric manifestations of Parkinson's disease (Review)

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Exp Ther Med. 2021 Sep;22(3):1010. doi: 10.3892/etm.2021.10443. Epub 2021 Jul 15.

ABSTRACT

Life expectancy has increased worldwide and, along with it, a greater prevalence of age-dependent disorders, chronic illnesses and comorbidities can be observed. In 2019, in both Europe and the Americas, dementias ranked 3rd among the top 10 causes of death. Parkinson's disease (PD) is the second most frequent type of neurodegenerative disease. In the last decades, globally, the number of people suffering from PD has more than doubled to over 6 million. Of all the neurological disorders, PD increased with the fastest rate. This troubling trend highlights the stringent need for accurate diagnostic biomarkers, especially in the early stages of the disease and to evaluate treatment response. To gain a broad and complex understanding of the recent advances in the '-omics' research fields, electronic databases such as PubMed, Google Academic, and Scie nce Direct were searched for publications regarding metabolomic studies on PD to identify specific biomarkers for PD, and especially PD with associated psychiatric symptomatology. Discoveries in the fields of metagenomics, transcriptomics and proteomics, may lead to an improved comprehension of the metabolic pathways involved in disease etiology and progression and contribute to the discovery of novel therapeutic targets for effective treatment options.

PMID:34345292 | PMC:PM C8311266 | DOI:10.3892/etm.2021.10443

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Systemic immune-inflammation index predicts a reduced risk of end-stage renal disease in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody-associated vasculitis: A retrospective observational study

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Exp Ther Med. 2021 Sep;22(3):989. doi: 10.3892/etm.2021.10421. Epub 2021 Jul 13.

ABSTRACT

Chronic inflammation has been indicated to be important in the pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). The systemic immune-inflammation index (SII) is a novel marker of inflammation. The present study was thus performed to explore the association between the SII at diagnosis and inflammatory response and disease activity in Chinese patients with myeloperoxidase (MPO)-AAV. Furthermore, it was evaluated whether the SII is able to predict the progression to end-stage renal disease (ESRD) and patient survival. A total of 190 patients with MPO-AAV were included in the present study. The baseline SII was positively correlated with C-reactive protein (CRP; r=0.274, P<0.0001) and the erythrocyte sedimentation rate (ESR; r=0.481, P<0.0001). However, the SII had no obvious correlation with the Birmingham vascu litis activity score. Patients with SII≥2,136.45 exhibited better cumulative renal survival rates than those with SII<2,136.45 (P=0.001). However, no significant difference in patient survival was indicated between patients with SII≥2,136.45 and those with SII<2,136.45 at diagnosis. In conclusion, the SII was positively correlated with CRP and ESR in Chinese patients with MPO-AAV. Furthermore, the SII may be an independent factor associated with a reduced risk of ESRD.

PMID:34345271 | PMC:PMC8311255 | DOI:10.3892/etm.2021.10421

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Overview of the pathogenesis of COVID-19 (Review)

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Exp Ther Med. 2021 Sep;22(3):1011. doi: 10.3892/etm.2021.10444. Epub 2021 Jul 15.

ABSTRACT

At present, the pathogenesis of the novel coronavirus disease 2019 (COVID-19) has not been fully elucidated. Clinical and experimental findings from studies investigating COVID-19 have suggested that the immune-inflammatory response has a crucial role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The present article aimed to systematically review the available literature on the pathogenesis of COVID-19. Severe COVID-19 is characterized by organ dysfunction, hypercytokinemia and lymphopenia. It is assumed that the direct cytopathological damage of host cells and the dysregulated immune response caused by SARS-CoV-2 may be the primary underlying mechanisms of COVID-19. Based on the published literature, this review attempts to provide an integrated view of the immunological mechanisms and the potential pathogenesis of C OVID-19, providing an in-depth summary of the host-pathogen interaction and host immune responses. It is of great importance to elucidate the possible pathogenesis of COVID-19 to determine the direction of future research.

PMID:34345293 | PMC:PMC8311250 | DOI:10.3892/etm.2021.10444

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Psoriasis beyond the skin: Ophthalmological changes (Review)

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Exp Ther Med. 2021 Sep;22(3):981. doi: 10.3892/etm.2021.10413. Epub 2021 Jul 12.

ABSTRACT

Psoriasis is a chronic, immune-mediated inflammatory disease of unknown etiology that may be associated with abnormal T-lymphocyte function. Ocular manifestations associated with psoriasis, particularly artropathic or pustular psoriasis, usually affect men, often during exacerbations of the disease. It has been reported that eye damage tends to occur later compared with cutaneous or joint manifestations, blindness being the most disabling complication. Previous studies have focused on ophthalmic manifestations and identified several etiopathogenic mechanisms. Psoriasis may be associated with eye complications such as lesions of the eyelids, conjunctiva and others, with systemic inflammation being the main contributor. In addition, the treatment used for psoriasis may cause ocular changes. The main ophthalmic manifestations associated with psoriasi s are keratoconjunctivitis sicca, blepharitis, conjunctivitis and uveitis. The treatment of uveitis, perceived as one of the most serious eye conditions, is controversial and has yet to be clearly determined. Thus, the aim of the present review was to emphasize the importance of regular eye examination for patients with psoriasis, either those receiving biological treatment or those not receiving treatment, in order to diagnose and manage the disease appropriately.

PMID:34345263 | PMC:PMC8311223 | DOI:10.3892/etm.2021.10413

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Tumor Volume Doubling Time in Active Surveillance of Papillary Thyroid Microcarcinoma: A Multicenter Cohort Study in Korea

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Thyroid, Ahead of Print.
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