Showing papers in "Balkan Medical Journal in 2021"

Hsa-miR-217 Inhibits the Proliferation, Migration, and Invasion in Non-small Cell Lung Cancer Cells Via Targeting SIRT1 and P53/KAI1 Signaling

Abstract: Background: Brain metastasis is a major cause of cancer death in patients with lung cancer. Sirtuin 1 and hsa-miR-217 have been identified to mediate the development of non-small cell lung cancer. Aims: To investigate the roles of hsa-miR-217, its target sirtuin 1, and the P53/KAI1 axis in the brain metastasis from non-small cell lung cancer. Study Design: Cell culture study. Methods: Human pulmonary adenocarcinoma brain metastasis cell line PC-14/B were incubated and treated with constructed lentiviral plasmids expressing miR-217 and/or sirtuin 1. BEAS-2B cell line was used as a control. The targeted regulation of miR-217 to sirtuin 1was examined using a dual-luciferase reporter assay. Cell proliferation, migration, invasion, and related protein expression were detected to examine the effect of the miR-217/sirtuin 1 expression on metastasis. Results: PC-14/B cells expressed higher sirtuin 1 and lower P53 and KAI1 compared with BEAS-2B control cells (p<0.05). Sirtuin 1 was a direct target of miR-217. MiR-217 expression suppressed PC-14/B cell invasion (p=0.004), migration (p=0.001), and proliferation (p<0.05), whereas sirtuin 1 overexpression reversed all processes. sirtuin 1 expression inhibited P53, KAI1/CD82, matrix metalloproteinase-9, and s-catenin but upregulated E-cadherin protein. MiR-217 overexpression induced reverse changes. Conclusion: Hsa-miR-217 and its target sirtuin 1 acted as metastasis suppressor and promoter gene in non-small cell lung cancer, respectively. The hsa-miR-217/sirtuin 1/P53/KAI1 metastasis regulatory pathway showed novel and crucial roles in brain metastasis from non-small cell lung cancer. This axis might be a potential target for the treatment of brain metastasis of lung cancer.

Metformin Attenuates Ischemia-reperfusion Injury of Fatty Liver in Rats Through Inhibition of the TLR4/NF-κB Axis

Abstract: Background Donor organs for liver transplantation may often have fatty liver disease, which confers a higher sensitivity to ischemia/reperfusion injury. At present, there is no effective treatment for the condition. Evidence has suggested that metformin, the first-line medication for diabetes, has protective effects against many disorders. However, the potential role of metformin in ischemia/reperfusion injury in fatty liver disease remains unclear. Aims To examine the effect of metformin treatment during ischemia/reperfusion injury in fatty liver and determine the possible mechanisms. Study Design Animal experimentation. Methods Sprague-Dawley male rats were fed a high-fat diet (520 kcal/100 g) for 14 weeks and then were subjected to the orthotopic autologous liver transplantation model. Sections of liver tissue were stained with hematoxylin and eosin to visualize the damage. Blood and liver samples were used to analyze the related proteins and components involved in the inflammatory signaling pathway. Results We found that metformin significantly ameliorated the ischemia/reperfusion injury of the fatty liver through a reduction in alanine aminotransferase/aspartate aminotransferase concentrations in the serum and a decrease in dead cells, as shown by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay (p<0.05). In addition, metformin significantly attenuated interleukin (IL)-6, IL-1β, and tumor necrosis factor-α production and increased the expression of active caspase-3 and Bax in the liver (p<0.05). Mechanistically, metformin suppressed the activation of toll-like receptor 4 (TLR4)/NF-κB signaling (p<0.05), resulting in a decreased inflammatory response and apoptosis. Conclusion Our findings demonstrated that metformin attenuated ischemia/reperfusion injury in fatty liver disease via the TLR4/NF-κB axis, suggesting that metformin could have potential therapeutic applications in ischemia/reperfusion injury associated with liver transplantation.

Detection of sasX Gene and Distribution of SCCmec Types in Invasive and Non-invasive Coagulase-negative Staphylococci

Abstract: Background Coagulase-negative staphylococci, which belong to the normal microbiota of the skin and mucous membranes, are opportunistic pathogens. sasX, a newly described protein, is thought to play an important role in nasal colonization and methicillin-resistant Staphylococcus aureus virulence, and it may be acquired from coagulase-negative staphylococci by horizontal gene transfer. It has been considered that understanding the function of sasX gene may help clarify the relevance of the different adhesion mechanisms in the pathogenesis of infections associated with biofilm. Aims To investigate the sasX gene presence, staphylococcal cassette chromosome mec types, and antimicrobial resistance patterns of invasive and noninvasive coagulase-negative staphylococci isolates. Study design Cross-sectional study. Methods The study included a total of 180 coagulase-negative staphylococci strains. Non-invasive isolates (n=91) were obtained from the hands of healthy volunteers who do not work at the hospital (n=30), the nasal vestibule of healthy volunteer hospital workers (n=26), and central venous catheter (n=35). Invasive isolates (n=89) were isolated from peripheral blood cultures of inpatients who do not have catheters. All isolates were identified by conventional microbiological methods, automated systems, and, if needed, with matrix-assisted laser desorption/ionization-time of flight. Staphylococcal cassette chromosome mec typing, sasX and mec gene detection, antibiotic susceptibility, and sasX gene sequence analysis were performed. Results Peripheral blood, central venous catheter colonization, and nasal vestibule isolates were positive for the sasX gene, whereas hand isolates were negative. sasX gene was present in 17 isolates, and no statistical significance was found between invasive and noninvasive isolates (p=0.173). Sequence analysis of the sasX genes showed high homology to related proteins of Staphylococcus phage SPbeta-like and Staphylococcus epidermidis RP62A. staphylococcal cassette chromosome mec type V was the most prevalent regardless of species. staphylococcal cassette chromosome mec type II was more frequent in invasive isolates and found to be statistically important for invasive and noninvasive S. epidermidis isolates (p=0.029). Staphylococcus haemolyticus isolates had the overall highest resistance rates. Resistance to ciprofloxacin, trimethoprim-sulfamethoxazole, and erythromycin was found to be higher in isolates from catheter and blood culture. Staphylococcus hominis isolates had the highest rate for inducible clindamycin resistance. None of the isolates were resistant to vancomycin, teicoplanin, and linezolid. Conclusion The sasX gene is detected in 9.44% of the isolates. There is no statistical difference between the sasX-positive and -negative isolates in terms of antibacterial resistance and the presence of sasX and SCCmec types. Further studies about the role of sasX at virulence in coagulase-negative staphylococci, especially from clinical samples such as tracheal aspirate and abscess isolates, and distribution of staphylococcal cassette chromosome mec types are needed.

A Promising, Novel Radiosensitizer Nanodrug Complex for Oral Cavity Cancer: Cetuximab and Cisplatin-Conjugated Gold Nanoparticles.

Abstract: BACKGROUND Nanomedicine has provided promising tools for the imaging, diagnosis, and treatment of cancer. Gold nanoparticles (GNPs) may be useful in enhancing the efficacy of radiotherapy, such as radiosensitization, in cancer therapy. AIMS To develop a nanodrug complex containing cetuximab (C225,CTX) and cisplatin (CDDP) conjugated with GNPs and to investigate its cytotoxic effects on oral cavity cancer cells when combined with radiotherapy. STUDY DESIGN In vitro cell culture study. METHODS The GNPs were synthesized and successfully conjugated with cetuximab and cisplatin. Cell viability was monitored by the xCELLigence real-time cell analysis (RTCA) single-plate (SP) system in GNP-treated UPCI-SCC-131 cells for 48 hours. Cells with/without GNPs were irradiated with 6 MV X-rays, and colony formation was assayed to investigate the long-term effects of GNPs and the nanodrug complex after irradiation on radiotherapy-resistant oral cavity cancer cells. RESULTS The GNPs entered the tumor cells, and GNP-CDDP (P <.0001) and GNP-CDDP-CTX (P < .0001) were shown to cause a decrease in cell viability. GNP and GNP-CTX combined with radiotherapy led to greater reduction on UPCI-SCC-131 colony numbers, than radiation alone (P = .0369) and radiation with free CTX, with sensitizing enhancement ratios of 1 : 2 and 1 : 9, respectively. CONCLUSION The cetuximab and cisplatin-conjugated gold nanodrug complex has a great potential to increase cytotoxicity and overcome resistance to radiotherapy, in the treatment of oral cavity cancer.

Comparison of BPAP S/T and Average Volume-Assured Pressure Support Modes for Hypercapnic Respiratory Failure in the Emergency Department: A Randomized Controlled Trial.

Abstract: Background There is limited research into the utility of average volume- assured pressure support (AVAPS), a volume-assured pressure-controlled mode, especially in patients with hypercapnic respiratory failure. Aims This study aimed at a randomized comparison of AVAPS and bilevel positive airway pressure spontaneous/timed (BPAP S/T) modes in non-invasive mechanical ventilation application with hypercapnic respiratory failure patients in the emergency department. Study design Randomized controlled study. Methods Eighty of 140 patients admitted to the emergency department with hypercapnic respiratory failure requiring non-invasive mechanical ventilation were randomly assigned to the AVAPS or S/T groups (33 patients in the S/T group, 47 patients in the AVAPS group) using the sealed envelope method. Data of arterial blood gas, vital parameters, Glasgow Coma Score, additional treatment needs, and clinical outcomes were evaluated, and the treatment success rates of both groups were compared. Results A total of 80 patients, 33 in the S/T and 47 in the AVAPS group, were analyzed in the study. The pH values improved in the AVAPS group compared to the baseline (0.07 [0.04-0.10] vs 0.03 [0.00-0.11]). PaCO2 (partial pressure of carbon dioxide) excretion was faster in the AVAPS group than in the S/T group in the first hour (10.20 mmHg [6.20-19.20] vs. 4.75 ([-] 0.83-16.88)). The comparison of blood gas measurements showed no significant differences between the groups regarding the changes in PaCO2 and pH values over time (P = .141 and P = .271, respectively). During the emergency department follow-up, 3 (6.4%) patients in the AVAPS group and 5 (15.2%) patients in the S/T group needed intubation [Relative risk: 0.42 (95% CI: 0.11 to 1.64), P = .21]. Conclusion The AVAPS mode is as effective and safe as BPAP S/T in treating patients with hypercapnic respiratory failure in the emergency department.

Quantitative Assessment of Salivary Gland Parenchymal Vascularization Using Power Doppler Ultrasound and Superb Microvascular Imaging: A Potential Tool in the Diagnosis of Sjögren’s Syndrome

Abstract: Background Primary Sjogren’s syndrome is a chronic inflammatory autoimmune disease. Minor salivary gland biopsy is the gold standard for the diagnosis of primary Sjogren’s syndrome. Superb microvascular imaging, power Doppler ultrasound, and color Doppler of the salivary glands represent non-invasive, non-irradiating modality for evaluating the vascularity of the salivary glands in the diagnosis and follow-up of primary Sjogren’s syndrome. Aims To evaluate the efficacy of superb microvascular imaging and vascularity index in salivary glands for the sonographic diagnosis of primary Sjogren’s syndrome. Study design Prospective case-control study. Methods Twenty participants with primary Sjogren’s syndrome and 20 healthy subjects were included in the study. Both parotid glands and submandibular glands were evaluated by superb microvascular imaging, power Doppler ultrasound, and color Doppler. The diagnostic accuracy of superb microvascular imaging was compared using these techniques. Results In the patient group, the vascularity index values of superb microvascular imaging in parotid glands and submandibular glands were 3.5±1.66, 5.06±1.94, respectively. While the same values were 1.0±0.98 and 2.44±1.34 in the control group (p≤0.001). In the patient group, the vascularity index values of power Doppler ultrasound in parotid glands and submandibular glands were 1.3±1.20 and 2.59±1.82, respectively. While the same values were 0.3±0.32 and 0.85±0.68 in the control group (p≤0.001). The superb microvascular imaging vascularity index cut-off value for the diagnosis of primary Sjogren’s syndrome in parotid glands that maximizes the accuracy was 1.85 (area under the curve: 0.906; 95% confidence interval: 0.844, 0.968), and its sensitivity and specificity were 87.5% and 72.5%, respectively. While the superb microvascular imaging vascularity index cut-off value for the diagnosis of primary Sjogren’s syndrome in submandibular gland that maximizes the accuracy was 3.35 (area under the curve: 0.873; 95% confidence interval: 0.800, 0.946), its sensitivity and specificity were 82.5% and 70%, respectively. Conclusion Superb microvascular imaging with high reproducibility of the vascularity index has a higher sensitivity and specificity than the power Doppler ultrasound in the diagnosis of primary Sjogren’s syndrome. It can be a noninvasive technique in the diagnosis of primary Sjogren’s syndrome when used with clinical, laboratory and other imaging methods.

Role of Plasma Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 and microRNA-98 in Severity and Risk of Coronary Artery Disease.

Abstract: BACKGROUND Coronary artery diseases are the most important cause of premature death, and these diseases are predominantly related to atherosclerosis. Soluble lectin-like oxidized low-density lipoprotein receptor-1 and microRNAs are closely associated with atherosclerotic coronary heart diseases. AIMS To investigate the relationship between the severity and risk of coronary artery disease and plasma soluble lectin-like oxidized low-density lipoprotein receptor-1 and miR-98. STUDY DESIGN Case-control study. METHODS Angiographically documented patients with 38 single-vessel, 75 double-vessel, and 62 multi-vessel coronary artery disease; 62 healthy control participants; and 24-hour hypoxic (1% oxygen) human umbilical vein endothelial cells were included in this study. Circulating soluble lectin-like oxidized low-density lipoprotein receptor-1 concentrations were determined through enzyme-linked immunosorbent assays, and miR-98 expressions were measured by quantitative real-time polymerase chain reaction. RESULTS The expressions of plasma soluble lectin-like oxidized low-density lipoprotein receptor-1 levels were progressively and significantly higher in patients with single-vessel, double-vessel, and multi-vessel coronary artery disease than in healthy controls (p<0.001). Circulating soluble lectin-like oxidized low-density lipoprotein receptor-1 concentrations in female patients with multi-vessel, double-vessel, and single-vessel coronary artery disease had evidently elevated compared with that in male patients (p<0.001). Plasma soluble lectin-like oxidized low-density lipoprotein receptor-1 levels were remarkably increased in females with coronary artery disease in different age groups compared with the males in the same age groups (p<0.001). Patients with single-vessel (areas under the curve=0.879), double-vessel (area under the curve=0.928), and multi-vessel (area under the curve=0.943) coronary artery disease have been clearly differentiated from healthy participants with respect to high sensitivity and specificity. The expression of miR-98 was noticeably downregulated in patients with single-, double- and multi-vessel occluded coronary artery disease and in hypoxic human umbilical vein endothelial cell compared with controls (p<0.001). Significantly elevated lectin-like oxidized low-density lipoprotein receptor-1 and caspase-3 activity and remarkably decreased cellular viability in hypoxic injured human umbilical vein endothelial cell. On the contrary, mimic of miR-98 markedly reduced caspase-3 and lectin-like oxidized low-density lipoprotein receptor-1 levels and highly increased cellular viability. CONCLUSION Elevated circulating plasma soluble lectin-like oxidized low-density lipoprotein receptor-1 levels have a potential impact to identify the severity of coronary artery disease and have a strong correlation with aging as well as the female gender. Reduced plasma miR-98 level is possibly considered a risk factor for coronary artery disease, and agomiR-98 prevents atherosclerosis and cellular injury by targeting lectin-like oxidized low-density lipoprotein receptor-1.

Comparison of Different Pharmaceutical Preparations of Colchicine in Children with Familial Mediterranean Fever: Is Colchicine Opocalcium a Good Alternative?

Abstract: BACKGROUND Colchicine is an anti-inflammatory agent used for preventing familial Mediterranean fever (FMF) attacks and amyloidosis. A significant number of patients are non-responsive or intolerant to the domestic drug colchicum dispert. AIMS To compare the efficacy and side effects of colchicum dispert and colchicine opocalcium in children with FMF. STUDY DESIGN A total of 29 children with FMF who used colchicum dispert for at least 6 months initially and colchicine opocalcium for another consecutive 6 months were included. Sex and gender equity in research was considered. Clinical features, visual analog scale for pain scores, exercise-induced leg pain, and FMF severity scores with laboratory parameters were evaluated for both the treatment periods. Bristol stool chart and number of stools per 24 hours were recorded to compare the gastrointestinal side effects. METHODS A total of 29 children with FMF who used colchicum dispert for at least 6 months initially and colchicine opocalcium for another consecutive 6 months were included. Sex and gender equity in research was considered. Clinical features, visual analog scale for pain scores, exercise-induced leg pain, and FMF severity scores with laboratory parameters were evaluated for both the treatment periods. Bristol stool chart and number of stools per 24 hours were recorded to compare the gastrointestinal side effects. RESULTS The major indication was non-responsiveness in 18 patients (62%) and intolerance in 11 patients (38%). Usage of colchicine opocalcium (significantly higher dosage than colchicum dispert) showed statistically significant beneficial effects on the number and duration of attacks, visual analog scale for pain, exercise-induced leg pain scores, and FMF severity scores (p<0.05 for each parameter). Bristol stool chart questionnaire scores decreased from 5.62±1.56 to 4.15±1.73 points, and the scores of daily stool number decreased from 0.46±0.894 to 0.03±0.118 points (p<0.05). There were 12 patients who benefited from the switch without a change in dosage, and the clinical features were significantly better with the colchicine opocalcium treatment. CONCLUSION Pediatric patients with FMF, who have active disease and/or gastrointestinal complaints during the use of colchicum dispert, may benefit from colchicine opocalcium.

Coronavirus Disease 2019 and Antibiotic Stewardship-Antibiotic Usage in Adult Patients: Is It Necessary? When Should It be Concerned?

Abstract: Antibiotic consumption rates were quite high in number, although the bacterial coinfection rates were low in coronavirus disease 2019 pneumonia. Generally, empirical antibiotic treatment is not recommended for uncomplicated coronavirus disease 2019 mild to moderate pneumonia cases. On the other hand, antibiotic treatment and de-escalation are recommended for intubated intensive care unit patients or critical patients with sepsis, septic shock, or acute respiratory distress syndrome. The presentation of patients with severe coronavirus disease 2019 pneumonia can direct the clinicians to use antibiotics. We believe that wait and watch strategy can be preferred in such cases without sepsis, secondary bacterial infection findings, or procalcitonin < 0.5 ng/ mL. We think that a new wave of resistance will occur inevitably if we cannot perform the antibiotic stewardship properly.