Effect of Bovine Lactoferrin Treatment on Iron Homeostasis and Gene Expression Changes in Multiple Organ Dysfunctions During Wound Healing Process in Rats.

BACKGROUND: Injury systemically disrupts the homeostatic balance and can cause organ failure. LF mediates both iron-dependent and iron-independent mechanisms, and the role of LF in regulating iron homeostasis is vital in terms of metabolism. OBJECTIVES: In this study, we evaluated the organ-level effect and gene expression change of bLf in the cutaneous repair process. MATERIALS AND METHODS: An excisional full-thickness skin defect (FTSD) wound model was created in male Sprague Dawley rats (180-250 g) (n = 48) fed a high-fat diet (HFD) and the PHGPx, SLC7A11 and SLC40A1 genes and iron metabolism were evaluated. The animals were randomly divided into 6 groups: 1- Control, 2- bLf (200 mg/kg/day, oral), 3- FTSD (12 mm in diameter, dorsal), 4- HFD + bLf, 5- HFD + FTSD, 6- HFD + FTSD + bLf. Histologically, iron accumulation was demonstrated by Prussian blue staining in the liver, kidney, and intestinal tissues. Gene expression analysis was performed with qPCR. RESULTS: Histologically, iron accumulation was demonstrated by Prussian blue staining in the liver, kidney, and intestinal tissues. Prussian blue reactions were detected in the kidney. PHPGx and SLC7A11 genes in kidney and liver tissue were statistically significant (P < 0.05) except for the SLC40A1 gene (P > 0.05). Expression changes of the three genes were not statistically significant in analyses of rat intestinal tissue (P = 0.057). CONCLUSION: In the organ-level ferroptotic damage mechanism triggered by wound formation. BLf controls the expression of three genes and manages iron deposition in these three tissues. In addition, it suppressed the increase in iron that would drive the cell to ferroptosis and anemia caused by inflammation, thereby eliminating iron deposition in the tissues.

Evaluation of mucin-1, nuclear factor κB, and hemoglobin A1c levels in obese and non-obese individuals.

OBJECTIVE: Obesity is a chronic multisystem disease associated with increased morbidity and mortality. Obesity, which is a complex, multifactorial, and heterogeneous condition, is thought to result from the interaction of environmental, physiological, and genetic factors. In this study, the relationship between serum levels of hemoglobin A1c, mucin-1, and nuclear factor κB in obese and healthy cohorts was evaluated along with biochemical and gene expressions and with demographic and clinical covariates, and their effects on obesity were evaluated. METHODS: This case-control study included a total of 80 individuals, 40 healthy controls and 40 obesity patients, consisting of female and male aged between 18 and 63 years. Hemoglobin A1c, mucin-1, and nuclear factor κB levels were determined by ELISA in serum samples obtained from patients. In addition, aspartate aminotransferase, alanine transaminase, low density lipoprotein, and glucose values were measured. The gene expressions of the same markers were analyzed by quantitative real-time polymerase chain reaction, and their regulation status was defined. RESULTS: Serum levels of hemoglobin A1c, mucin-1, and nuclear factor κB were found to be high in obese individuals (p<0.05). The gene expression of these serum markers was found to be upregulated. Of the anthropometric measurements, waist circumference and body mass index were correlated with both serum markers and gene expressions (p<0.05). CONCLUSION: In addition to the known association of hemoglobin A1c and nuclear factor κB with obesity, serum levels of mucin-1 as well as upregulation of genes point to its modifier effect on obesity. These parameters can be the powerful markers in the diagnosis of obesity.

Thymoquinone ameliorates symptoms of Parkinson's disease in a 6-OHDA rat model by downregulation of miR-204-3p.

microRNAs (miRNAs) play a significant role in the pathophysiology of Parkinson's disease. In this study, we evaluated the neuroprotective effect of thymoquinone on the expression profiles of miRNA and cognitive functions in the 6-hydroxydopamine (6-OHDA)-induced Parkinson's model. Male adult Wistar albino rats (200-230 g, n  = 36) were randomly assigned to six groups: Sham, thymoquinone (10 mg/kg, p.o.), 6-OHDA, 6-OHDA + thymoquinone (10 mg/kg), 6-OHDA + thymoquinone (20 mg/kg), and 6-OHDA + thymoquinone (50 mg/kg). Behavioral changes were detected using the open field and the elevated plus maze tests. The mature 728 miRNA expressions were evaluated by miRNA microarray (GeneChip miRNA 4.0). Ten miRNAs were selected (rno-miR-212-5p, rno-miR-146b-5p, rno-miR-150-5p, rno-miR-29b-2-5p, rno-miR-126a-3p, rno-miR-187-3p, rno-miR-34a-5p, rno-miR-181d-5p, rno-miR-204-3p, and rno-miR-30c-2-3p) and confirmed by real-time PCR. Striatum samples were stained with hematoxylin-eosin to determine the effect of dopaminergic lesions. One-way ANOVA test and independent sample t -test were used for statistical analyses. rno-miR-204-3p was upregulated at 6-OHDA and downregulated at the 50 mg/kg dose of thymoquinone. In conclusion, thymoquinone at a dose of 50 mg/kg ameliorates symptoms of Parkinson's disease in a 6-OHDA rat model by downregulation of miR-204-3p. Also, the results showed that thymoquinone can improve locomotor activity and willing exploration and decreased anxiety. Therefore, thymoquinone can be used as a therapeutic agent.

Image-Assisted Pleural Needle Biopsy or Medical Thoracoscopy: Which Method for Which Patient? A Randomized Controlled Trial.

BACKGROUND: Image-guided or assisted needle biopsies and the increasing use of medical thoracoscopy (MT) have increased the diagnostic accuracy of pleural diseases significantly. However, no consensus exists regarding which patients with pleural effusion should undergo MT and which patients should undergo image-guided or assisted needle biopsy as the first procedure to ensure greater diagnostic accuracy. RESEARCH QUESTION: Which biopsy method is more appropriate for which patient to provide the highest diagnostic accuracy in the diagnosis of pleural effusion? STUDY DESIGN AND METHODS: This prospective, randomized, parallel study included 228 patients with undiagnosed exudative pleural effusion. Patients were divided into two groups based on CT scan findings. Group 1 included patients with pleural effusion only. Group 2 included patients with pleural thickening or lesion in addition to pleural effusion. Patients in each group were assigned randomly to an image-assisted Abrams needle pleural biopsy (IA-ANPB) or MT arm. The diagnostic sensitivity, reliability, and safety were determined for both groups. RESULTS: The false-negative rate was 30.3% for the IA-ANPB arm and 3.1% for the MT arm in group 1. The same rates were 11.9% for IA-ANPB and 4.7% for MT in group 2. In group 1, the sensitivity for the IA-ANPB arm was 69.7%, and the negative likelihood ratio was 0.30. The same rates for the MT arm were 96.9% and 0.03 (P = .009). In group 2, these values were 88.1% and 0.12 for the IA-ANPB arm and 95.4% and 0.05 for the MT arm (P = .207). The rate of complications between the two biopsy methods was not different (8.5% and 15.8%, respectively; P = .107). INTERPRETATION: MT showed a high diagnostic success in all patients with pleural fluid. However, IA-ANPB showed similar diagnostic success as MT in patients with pleural effusion and associated pleural thickening or lesions. Therefore, in the latter case, IA-ANPB could be preferable to MT. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT05428891; URL: www. CLINICALTRIALS: gov.

PTZ-kindled rat model; evaluation of seizure, hippocampal EGR-1, and Rev-erbα gene regulation, behavioral analysis, and antioxidant capacity of Gum Arabic.

BACKGROUND: Epilepsy is a neurological disease characterized by recurrent seizures, hyperexcitable neurons and various behavioral comorbidities. The electrical charge during seizures depletes the antioxidant defense mechanism in the epileptic brain and increases the oxidative burden. Natural antioxidant compounds are potential therapeutics in the treatment of two major pathologies of epilepsy with their anticonvulsant and anxiolytic effects and can modulate these targets. Gum Arabic is one of the natural plant polysaccharides that is non-toxic and biodegradable. METHODS AND RESULTS: A total of 30 Wistar albino male rats (8-12 weeks, 350-500 g), were randomly divided into 5 groups with 6 animals in each group: 1-Control, 2-Sham (Phosphate buffer saline (PBS)), 3-PTZ, 4-Gum Arabic, 5-PTZ + Gum Arabic. PTZ was administered i.p at 35 mg/kg/day for 11 days. After 48 h, the injection was completed with 75 mg/kg PTZ. Locomotor activity, immobilization, rearing, grooming, eating, and drinking behaviors were recorded with the LABORAS behavior system for 30 min after kindling. Animals were treated with Gum Arabic (2 mg/kg/day, oral gavage) for 10 days. At the end of the period, animal behavior was recorded again. Then the hippocampus tissues were removed. Oxidative parameters (TAS and TOS), early growth response 1 (EGR1) and nuclear receptor subfamily 1 group D member 1 (Rev-erbα) gene expressions and behaviors were analyzed. CONCLUSION: Gum Arabic increased TAS levels (P = 0.000), decreased TOS levels (P = 0.000), and thus exhibited antioxidant properties by reducing oxidative stress burden. EGR1, which was upregulated in the seizure group, was downregulated after treatment (P = 0.000), and Rev-erbα was downregulated in seizure and upregulated after treatment (P = 0.000). Gum arabic may be an antiepileptic and anxiolytic therapeutic in improving epileptic seizures by reducing oxidative stress burden through EGR1 and Rev-erbα.0.

Ferroptotic Potency of ISM1 Expression in the Drug-Induced Alzheimer's Disease-Like Phenotype Under the Influence of Betulin.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by two main pathological mechanisms, mostly hyperphosphorylated tau and amyloid-ß toxicity. Although many studies focus on these basic mechanisms, ferroptosis draws attention as an important pathway responsible for neurodegeneration in AD. There is no definitive treatment for AD but alternative phytochemicals to drugs come into prominence. Betulin is usually obtained from the birch tree. It is an abundant triterpene and has a high antioxidant capacity. Isthmin-1 (ISM1) is a secreted adipokine. OBJECTIVE: In this study, we investigated the potential treatment of AD in the ferroptosis-ISM1-betulin triangle. METHODS: For this, we created an AD model with okadaic acid (200 ng/kg)) in 36 Wistar albino male rats and treated with betulin (20 mg/kg/day, i.p). We evaluated ISM1 gene expression, iron accumulation, and total oxidative metabolism parameters (TAS, TOS, OSI) in hippocampal tissue. We analyzed cognitive recovery in AD with Morris Water Maze Test and general locomotor activity, explore, and anti-anxiolytic effect with Open Field Test. RESULTS: We compared the obtained data with metabolic and genetic results. In conclusion, betulin may have a role in neuronal ferroptotic mechanisms by reducing iron accumulation by ISM1 regulation. CONCLUSIONS: Betulin may have a role in neuronal ferroptotic mechanisms by reducing iron accumulation by ISM1 regulation. Although this study suggests the corrective effect of betulin and ISM1 on cognitive gain and anxiety, it is the first study to show the total antioxidant capacity of betulin in AD.

Deep phenotyping of miRNAs in exercise-induced cardiac hypertrophy and fibrosis.

Cardiac hypertrophy (CH) is an adaptational enlargement of the myocardium, in exposure to altered stress conditions or in case of injury which can lead to heart failure and death. MicroRNAs (miRNAs) are noncoding RNAs that play a significant role in modulating gene expression. Here, we aimed to identify new miRNAs effective in an experimental CH model and to find an epigenetic biomarker that could demonstrate therapeutic targets responsible for the pathology of heart tissue and serum. In this study, Sprague-Dawley male rats were divided into the training group (TG, n=9) and the control group (CG, n=6). Systolic and diastolic dimensions of the left ventricle and myocardial wall thickness were measured by echocardiography to assess CH. After the exercise program of the rats, miRNA expression measurements and histological analyses were performed. The 25,000 genes in the rat genome were searched using microarray analysis. A total of 128 miRNAs were selected according to the fold change rates, and nine miRNAs were validated for expression analysis. The terminal deoxynucleotidyl transferase dUTP nick (TUNEL) method was used to detect apoptotic cells. Cell proliferation was evaluated by the proliferative cell nuclear antigen (PCNA) method. Necrosis, bleeding, and intercellular edema were detected in TG. The mean histopathological score was higher in TG (p=0.03). There were rarely positive cells for apoptosis of both groups in cardiomyocytes. In the receiver characteristic curve analysis (ROC), the heart tissue rno-miR-290 had an area under the curve (AUC) of 0.920 with 100% sensitivity and 89.90% specificity (p=0.045), rno-miR-194-5p had AUC of 0.940 with 83.33% sensitivity and 100% specificity (p=0.003), and the serum rno-miR-132-3p AUC was 0.880 with 66.67% sensitivity and 100% specificity (p=0.004) in TG. miR-194-5p was used as a therapeutic target for remodeling the cardiac process. While miR-290 contributes to CH as a negative regulator, miR-132 in serum is effective in the pathological and physiological cardiac remodeling process and is a candidate biomarker.

Okadaic Acid-Induced Alzheimer's in Rat Brain: Phytochemical Cucurbitacin E Contributes to Memory Gain by Reducing TAU Protein Accumulation.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive decline, with hallmark pathologies related to amyloid beta (Aß) and TAU. Natural phytochemicals show promise for drug discovery to fill the current therapeutic innovation gap in AD. This study investigated the effect of cucurbitacin E (CuE), one of the bioactive components of Ecballium elaterium, on TAU fibril formation in okadaic acid-induced AD in rats. In a randomized design, we assigned 30 female Sprague Dawley rats to one of five experimental groups: (1) control, (2) stereotaxic surgery, (3) stereotaxic surgery + artificial cerebrospinal fluid, (4) stereotaxic surgery + okadaic acid (AD model), and (5) stereotaxic surgery + okadaic acid + CuE treatment. For experimental groups 4 and 5, rats were administered OKA-ICV (200 ng/kg) followed by CuE (4 mg/[kg·day], intraperitoneally) for 20 days. Expression of the MAPK1/3 and MAPK14 genes associated with TAU metabolism, hippocampal protein levels of these genes, cognitive functions of the rats, and histological accumulation of TAU in the brain were evaluated. Our findings in this preclinical model collectively suggest that phytochemical CuE contributes to memory gain by reducing TAU protein accumulation, which warrants further evaluation in future in vitro and in vivo studies.

The holistic approach to the CHRNA7 gene, hsa-miR-3158-5p, and 15q13.3 hotspot CNVs in migraineurs.

Migraine is a neurological disease characterized by severe headache attacks. Combinations of different genetic variations such as copy number variation (CNV) in a gene and microRNA (miRNA) expression can provide a holistic approach to the disease as a pathophysiological, diagnostic, and therapeutic target. CNVs, the Cholinergic Receptor Nicotinic Alpha 7 Subunit (CHRNA7) gene, and expression of gene-targeting miRNAs (hsa-miR-548e-5p and hsa-miR-3158-5p) in migraineurs (n = 102; with aura, n = 43; without aura, n = 59) and non-migraines (n = 120) aged 15-60 years, comparative, case-control study was conducted. Genetic markers were compared with biochemical parameters (BMI, WBC, Urea, GFR, ESR, CRP, HBG). All analyzes were performed by quantitative Real-Time PCR (q-PCR) and fold change was calculated with the 2-ΔΔCT method. The diagnostic power of the CHRNA7 gene, CNV, and miRNAs were analyzed with the receiver operating curve (ROC). CHRNA7 gene and hsa-miR-3158-5p are down-regulated in migraineurs and the gene is controlled by this miRNA via CNVs (p < .05). Both deletion and duplication were detected in patients with migraine for CVN numbers (p = .05). The number of CNV deletions was higher than duplications. When CHRNA7-CNV-hsa-miR-3158-5p was modeled together in the ROC analysis, the area under the curve (AUC) was 0.805, and the diagnostic power was "good". In migraineurs, the CHRNA7 gene can be controlled by hsa-miR-3158-5p via CNVs to modulate the mechanism of pain. These three genetic markers have diagnostic potential and may be used in antimigraine treatments.

Sinapic Acid Attenuated Cisplatin-Induced Cardiotoxicity by Inhibiting Oxidative Stress and Inflammation with GPX4-Mediated NF-kB Modulation.

The use of cisplatin is severely limited by the risk of developing cardiovascular complications. Sinapic acid may reduce cisplatin's side effects. The anti oxidant, anti-inflammatory, and peroxynitrite-scavenging properties of sinapic acid could provide protection against the cardiotoxicity caused by cisplatin. To induce toxicity in rats, cisplatin was administered for a period of 5 weeks. Animal electrocardiograms were obtained after cisplatin toxicity had taken effect. Blood samples and heart tissues were then harvested from the anesthetized animals. The ELISA technique was used to evaluate the level of proinflammatory cytokines and oxidative and nitrosative stress indicators in the heart tissue and serum. A real-time PCR was used to analyze GPX4 and NF-κB expression in the heart tissue. Hematoxylin-eosin and Masson's trichrome were also utilized. Electrocardiograms data showed an increase in QRS and QT intervals. Biochemically, cisplatin increased oxidative, nitrosative, and proinflammatory cytokine levels. Animals exposed to cisplatin had histopathological findings in the heart tissue, according to the results of histological assessment. Sinapic acid reduced TNF-alpha, interleukin-6, malondialdehyde, and ischemia-modified albumin. Sinapic acid also reduced oxidative and nitrosative stress. Furthermore, Sinapic acid restored lengthy QT and QRS. Cisplatin-treated rats had higher NF-κB activation than controls. This effect was successfully inhibited by sinapic acid. Histopathologically, tissues treated with sinapic acid were less damaged than tissues treated with cisplatin. In conclusion, our results suggest that sinapic acid exhibited a protective effect against the cardiotoxicity induced by cisplatin. These effects may be caused by the overexpression of GPX4 and the downregulation of NF-KB, as well as antioxidant and anti-inflammatory properties.

Downregulatory effect of miR-342-3p on epileptogenesis in the PTZ-kindling model.

BACKGROUND: Epileptogenesis is a process that results in neurons firing abnormally, causing seizures. Increasing evidence has shown that miRNAs expressed in the epileptic hippocampus are involved in epileptogenesis. We demonstrated the expression changes of miRNAs that may be effective in epileptogenesis in silico analysis in the kindling model created with Pentylenetetrazole (PTZ). Thus, we aimed to identify the target genes responsible for epileptogenesis. METHODS AND RESULTS: Fifteen male Wistar-albino rats (200-230 g) were randomly divided into two groups control (n = 6) and PTZ (n = 9). The control group received 0.5 ml saline, and the PTZ group (35 mg/kg i.p.) intraperitoneally (i.p.) (11 times, every other day) to induce tonic-clonic seizures. Seizures were observed and scored 30 min after PTZ injection. After the last dose of PTZ (75 mg/kg) administration, the hippocampus tissues of the rats were removed by anesthesia. Analysis of miRNAs was performed with the Affymetrix gene chip miRNA sequence (728 miRNA) and confirmed by the Real-Time Polymerase Chain Reaction (Real-Time PCR) method (29 miRNAs). We evaluated the expression change of the target gene of miRNA, whose expression change was detected using in silico analysis, by q-RT PCR. Eight miRNAs with changes in expression were detected. Of these miRNAs, miR-342-p was downregulated in the PTZ group and was statistically significant (p < 0.005). Ultimately, we determined that the target gene of miR-342-p is a metabotropic glutamate receptor 2 (GRM2) and that GRM2 expression is upregulated. CONCLUSIONS: Downregulation of miR-342-3p in the PTZ kindling model may result in the upregulation of GRM2.

miR-181a-5p is a potential candidate epigenetic biomarker in multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination and axonal degeneration. Abnormal expression of microRNAs (miRNAs) plays an important role in MS pathology. In this cohort study, differential expression of the four miRNAs (hsa-miR-155-5p, hsa-miR-9-5p, hsa-miR-181a-5p, and hsa-miR-125b-5p) was investigated in 69 individuals, including 39 MS patients (relapsing-remitting MS (RRMS), n = 27; secondary progressive MS (SPMS), n = 12) and 30 healthy controls. In silico analyses revealed possible genes and pathways specific to miRNAs. Peripheral blood miRNA expressions were detected by quantitative real-time PCR (qPCR). hsa-miR-181a-5p was downregulated and associated with increased MS risk (P = 0.012). The other three miRNAs were upregulated and not associated with MS (P < 0.05). The area under the curve (AUC) is 0.779. In silico analyses showed that hsa-miR-181a-5p may participate in MS pathology by targeting MAP2K1, CREB1, ATXN1, and ATXN3 genes in inflammation and neurodegeneration pathways. The circulatory hsa-miR-181a-5p can regulate target genes, reversing the mechanisms involved in MS pathologies such as protein uptake and processing, cell proliferation and survival, inflammation, and neurodegeneration. Thus, this miRNA could be used as an epigenomic-guided diagnostic tool and for therapeutic purpose.

Evaluation of Exudative Pleural Effusions: A Multicenter, Prospective, Observational Study.

PURPOSE: The aim of this study is to determine the diagnostic performances of pleural procedures in undiagnosed exudative pleural effusions and to evaluate factors suggestive of benign or malignant pleural effusions in tertiary care centers. METHODS: This was a multicenter prospective observational study conducted between January 1 and December 31, 2018. A total of 777 patients with undiagnosed exudative pleural effusion after the initial work-up were evaluated. The results of diagnostic procedures and the patients' diagnoses were prospectively recorded. Sensitivity, specificity, and accuracy estimates with 95% confidence intervals were used to examine the performance of pleural procedures to detect malignancy. RESULTS: The mean age ± SD of the 777 patients was 62.0 ± 16.0 years, and 68.3% of them were male. The most common cause was malignancy (38.3%). Lung cancer was the leading cause of malignant pleural effusions (20.2%). The diagnostic sensitivity and accuracy of cytology were 59.5% and 84.3%, respectively. The diagnostic sensitivity of image-guided pleural biopsy was 86.4%. The addition of image-guided pleural biopsy to cytology increased diagnostic sensitivity to more than 90%. Thoracoscopic biopsy provided the highest diagnostic sensitivity (94.3%). The highest diagnostic sensitivity of cytology was determined in metastatic pleural effusion from breast cancer (86.7%). CONCLUSION: The diagnostic performance increases considerably when cytology is combined with image-guided pleural biopsy in malignant pleural effusions. However, to avoid unnecessary interventions and complications, the development of criteria to distinguish patients with benign pleural effusions is as important as the identification of patients with malignant pleural effusions.

Investigation of the relationship of CO-RADS and CT patterns with laboratory parameters in COVID-19 patients and a new perspective on the total CT scoring system.

BACKGROUND: It is important to determine the correlation of the CO-RADS classification and computed tomography (CT) patterns of the lung with laboratory data. To investigate the relationship of CO-RADS categories and CT patterns with laboratory data in patients with a positive RT-PCR test. We also developed a structured total CT scoring system and investigated its correlation with the total CT scoring system. METHOD: The CT examinations of the patients were evaluated in terms of the CO-RADS classification, pattern groups and total CT score. Structured total CT score values were obtained by including the total CT score values and pattern values in a regression analysis. The CT data were compared according to the laboratory data. RESULTS: A total of 198 patients were evaluated. There were significant differences between the CO-RADS groups in terms of age, ICU transfer, oxygen saturation, creatinine, LDH, D-dimer, high-sensitivity cardiac troponin-T (hs-TnT), CRP, structured total CT score values, and total CT score values. A significant difference was also observed between the CT pattern groups and oxygen saturation, creatinine and CRP values. When the structured total CT score values and total CT score values were compared they were observed to be correlated. CONCLUSIONS: Creatinine can be considered as an important marker for the CO-RADS and pattern classifications in lung involvement. LDH can be considered as an important marker of parenchymal involvement, especially bilateral and diffuse involvement. The structured total CT scoring system is a new system that can be used as an alternative.

Biomarker potential of hsa-miR-145-5p in peripheral whole blood of manic bipolar I patients.

OBJECTIVE: Bipolar I disorder (BD-I) is a type of bipolar spectrum disorder characterized by manic or mixed episodes. Detecting microRNA regulations as epigenetic actors in BD-I is important to elucidate the pathogenesis of the disease and reveal the potential of microRNAs (miRNAs) as biomarkers. METHODS: We evaluated the expression profile of six candidate miRNAs (hsa-miR-145-5p, hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p, and hsa-miR-4725) in patients with BD-I and in healthy controls (aged 11-50 years). We also determined the potential target genes of these miRNAs through in silico analysis. The diagnostic values of the miRNAs were calculated through receiver operating characteristic curve analysis. RESULTS: Four miRNAs were upregulated (hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p) and hsa-miR-145-5p was downregulated in patients (p < 0.001). The target gene analyses showed that hsa-miR-145-5p specifically targets the dopamine decarboxylase (DDC) gene. The area under the curve of hsa-miR-145-5p was 0.987. CONCLUSION: Differential expression of five miRNAs in peripheral blood may be associated with the pathogenesis of BD-I, and hsa-miR-145-5p has potential as a BD-I biomarker. This miRNA can be used in dopamine-serotonin regulation and dose adjustment in drug therapy via the DDC gene.

Pentylenetetrazole-induced kindling rat model: miR-182 and miR-27b-3p mediated neuroprotective effect of thymoquinone in the hippocampus.

OBJECTIVES: Epilepsy is a neurological disease that pathologically affects brain functions. The epileptic hippocampus has modified microRNA(miRNA) levels. Therefore, we aimed to evaluate the neuroprotective effect of thymoquinone (TQ) in PTZ-induced epilepsy and to demonstrate the overlap between miRNA and mRNA expression profiles. METHODS: Male adult Wistar albino rats (200-230 g, n = 20) were divided into three groups as control (n = 6), PTZ (n = 7), and TQ + PTZ (n = 7). The PTZ kindling model was created by injecting PTZ in sub convulsive doses to rats on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, and 24 of the study into animals. Clonic and tonic seizures were induced by injecting a convulsive dose of PTZ on day 26 of the study. Rats in the TQ+PTZ group were treated by oral gavage with a 20 mg/kg TQ 2 h before each PTZ injection. The rats in the control group were treated with 0.5 ml saline. Seizure severity was evaluated with the Racine scale. The genes and signaling pathways targeted by miRNAs were determined by bioinformatics analysis. RESULTS: In the rat hippocampus, mature 728 miRNAs were analyzed by microarray and the nine miRNA were verified by quantitative Real-Time PCR. rno-miR-182 and rno-miR-27b-3p were up-regulated in the PTZ group and down-regulated in the TQ + PTZ group. DISCUSSION: In the PTZ kindling epilepsy model, the expression of these two miRNAs was regulated by TQ and exerted a neuroprotective effect by controlling the activities of target genes.

Correlation of Indeterminate Lesions of COVID-19 Pneumonia Detected on Computed Tomography with RT-PCR Results.

BACKGROUND: The typical findings of COVID-19 pneumonia include multilobar groundglass opacities and consolidation areas observed predominantly in the basal and peripheral parts of both lungs in computed tomography. OBJECTIVE: The current study aimed to correlate indeterminate lesions of COVID-19 pneumonia detected on computed tomography with the results of the reverse transcription-polymerase chain reaction (RT-PCR) test. METHODS: Patients with high-resolution computed tomography images that were reported to contain indeterminate lesions in terms of COVID-19 pneumonia were included retrospectively in the study. The lesions were categorized and the patterns were classified. The RT-PCR-positive and the RTPCR- negative patients were compared. P<0.05 was accepted as the statistical significance limit. RESULTS: The RT-PCR-positive patients exhibited a higher rate of peripheral lesions. Limited consolidation areas were not detected in the RT-PCR-positive patients. In the RT-PCR-negative patients, the rates of acinar nodules and the tree-in-bud pattern were significantly higher. The RTPCR- negative patients had higher nodular contour features and lesion coalescence. In the subgroup consisting of lesions with ground-glass opacities and/or ground-glass opacity around the nodule, the rate of nodular contour positivity was significantly higher in the RT-PCR- positive patients. CONCLUSION: COVID-19 pneumonia should be suspected when peripheral indeterminate lesions are detected. When indeterminate lesions, such as tree-in-bud pattern, acinar nodules and limited consolidation area are detected, alternative diagnoses should be considered first, even if there are ground glass opacities accompanying these lesions.

Evaluation of the contribution of fine-needle non-aspiration cytology to diagnosis in cases with pulmonary malignant lesions.

BACKGROUND: Fine-needle non-aspiration cytology (FNNAC) is an easy-to-apply, minimally invasive diagnostic method that contributes to the diagnosis and staging of lung cancer. FNNAC can be performed from peripheral lymph nodes as well as in peripheral lung lesions. This study aimed to evaluate the contribution of FNNAC performed from peripheral lesions or lymph nodes to diagnosis in patients with pulmonary malignant lesions. METHODS: FNNAC was applied from a peripherally located mass in the lung, chest wall lesion, or peripheral lymph node using a needle without an injector or active suction. The collected material was evaluated using the cytoblock method. The FNNAC accuracy was obtained by dividing the true positivity value by a number of needle biopsies performed. The 95% confidence interval of the obtained rate was also calculated. RESULTS: The mean age of 56 patients, two female (3.6%) and 54 male (96.4%), was 63.9 ± 9.1 (38-80) years. FNNAC was performed from the peripheral lymph node in 48 patients, the peripheral pulmonary lesion in four, and the accompanying chest wall lesion in four. While true positivity was present in 42 patients, two patients had true negativity, and 12 had false negativity. In five of the 12 cases reported as false negative, the collected material was evaluated as insufficient, while the malignant diagnoses of the remaining seven cases were confirmed by other diagnostic methods. The diagnostic success of FNNAC was determined as 78.57% (95% CI: 65.56-88.41). FNNAC was more successful in diagnosis when performed from the peripheral lymph node compared to the peripheral pulmonary lesion (p=0.033).

Screening for Copy Number Variations of the 15q13.3 Hotspot in CHRNA7 Gene and Expression in Patients with Migraines.

BACKGROUND: a migraine is a neurological disease. Copy number variation (CNV) is a phenomenon in which parts of the genome are repeated. We investigated the effects of the CNV and gene expression at the location 15q13.3 in the Cholinergic Receptor Nicotinic Alpha 7 Subunit (CHRNA7) gene, which we believe to be effective in the migraine clinic. METHODS: we evaluated changes in CHRNA7 gene expression levels and CNV of 15q13.3 in patients with migraine (n = 102, with aura, n = 43; without aura, n = 59) according to healthy controls (n = 120) by q-PCR. The data obtained were analyzed against the reference telomerase reverse transcriptase (TERT) gene with the double copy number by standard curve analysis. Copy numbers were graded as a normal copy (2), gain (2>), and loss (<2). RESULTS: we analyzed using the 2-ΔΔCT calculation method. The CHRNA7 gene was significantly downregulated in patients (p < 0.05). The analysis of CNV in the CHRNA7 gene was statistically significant in the patient group, according to healthy controls (p < 0.05). A decreased copy number indicates a dosage loss. However, no significant difference was observed among gain, normal, and loss copy numbers and expression values in patients (p > 0.05). The change in CNV was not associated with the downregulation of the CHRNA7 gene. CONCLUSION: Downregulation of the CHRNA7 gene may contribute to the formation of migraine by inactivation of the alpha-7 nicotinic receptor (α7nAChR). The association of CNV gains and losses with migraines will lead to better understanding of the molecular mechanisms and pathogenesis, to better define the disease, to be used as a treatment target.

Association of NRG3 and ERBB4 gene polymorphism with nicotine dependence in Turkish population.

BACKGROUND: Nicotine dependence (ND) is characterized by regular smoking, anxiety, irritation, difficulty concentrating, impatience, restlessness, tremor, dizziness, hunger, nicotine demand, and the individual's reluctance to quit despite knowing the health risks of smoking. Recently, it has been reported that the Neuregulin 3 (NRG3)/Erb-B2 receptor tyrosine kinase 4 (ERBB4) signaling pathway plays a role in ND. NRG3, which is activated after nicotine intake, binds to ERBB4 and causes GABA release. GABA reduces anxiety and tension, which are one of the nicotine withdrawal symptoms. Therefore we aimed to investigate the relationship between NRG3 and ERBB4 gene polymorphisms and ND. MATERIALS AND METHODS: The study population was comprised of patients with ND (n = 200) and healthy non-smoker control subjects (n = 200) who were matched for age, sex, and compared for comorbidity factors such as alcohol, smoking, duration, and education (age range 18-60). Genotypes were detected by Real-Time PCR using TaqMan technology. The Fagerström Nicotine Dependence Test (FTND) score was 5 and above for the patient group and 0 for the control group. DNA was obtained from whole peripheral blood and six polymorphisms of Neuregulin 3 (NRG3) (rs1836724, rs7562566, and rs10048757) and Erb-B2 Receptor Tyrosine Kinase 4 (ERBB4) (rs1764072, rs6584400, and rs10883934) genes were analyzed by real-time PCR method. RESULTS: Our findings show that the six selected SNPs are not significantly associated with ND in the Turkish population and no correlation with dependence levels (p > 0.05). CONCLUSION: Although our findings do not show a relationship between ND and these polymorphisms, it is the first study to investigate these single nucleotide polymorphisms (SNPs) for the first time in ND and to find some genotypes in the Turkish population when compared to other populations. Also, our findings are important in terms of their contribution to the literature and forensic genetics.