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Objectıves The objectives of this study were a) to investigate the effect of targeting the PANoptosome with 3,4-methylenedioxy-β-nitrostyrene (MNS) on PANoptosis in the Renal ischemia-reperfussion (RIR) model b) to investigate the kidney protective effect of MNS toward RIR injury. Methods Thirty-two rats were divided into four groups randomly. The groups were assigned as Control, Sham, DMSO (dimethyl sulfoxide) and MNS groups. The rats in the MNS group were intraperitoneally given 20 mg/kg of MNS 30 minutes before reperfusion. 2% DMSO solvent that dissolves MNS were given to the rats in DMSO group. Left nephrectomy was performed on the rats under anesthesia at the 6th hour after reperfusion. Glutathione peroxidase (GPx), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and 8-Okso-2′-deoksiguanozin (8-OHdG) levels were measured. Immunohistochemical analysis, electron microscopic and histological examinations were carried out in the tissues. Results Total tubular injury score was lower in the MNS group (p 0.05) in all groups. MNS considerably improved the tissue structure, based on the electron microscopic analysis. Conclusıons Our results suggested that MNS administrated before the reperfusion reduces pyroptosis, apoptosis and necroptosis. These findings suggest that MNS significantly protects the kidney against RIR injury by reducing PANoptosis as a result of specific inhibition of Nod-like receptor pyrin domain-containing 3 (NLRP 3), one of the PANoptosome proteins.

Objective:In our study, it was aimed to make the chemical analysis of hardaliye products (H1 and H2), which are commercially available by different manufacturers, and to examine their antioxidant and antimicrobial activities.Methods:Antioxidant activity, organic acid and phenolic compounds, and antimicrobial activity in Hardaliye products (H1 and H2) were determined by using 1.1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, [liquid chromatography-high resolution mass spectrometry (LC-HR/MS)] and liquid microdilution methods, respectively.Results:Ascorbic acid and fumaric acid from organic acids were determined by chemical analysis of hardaliye samples by LC-HR/MS method. While ascorbic acid concentrations were 21.295 mg/L and 26.84 mg/L in H1 and H2, respectively, fumaric acid concentrations were 59.55 mg/L in H1, and 224.562 mg/L in H2. While the phenolic component with the highest concentration in H1 was resveratrol (44.57 mg/L), it was observed that the phenolic component with the highest concentration in H2 was p-coumaric acid (31.87 mg/L). In terms of antioxidant activity, diphenyl-2-picrylhydrazylfree radical scavenging activity of hardaliye samples was determined as 2.07±0.004% and 2.49±0.004% in H1 and H2, respectively. It was determined that hardaliye samples showed inhibitory effect [H1 minimum inhibitor concentration (MIC): 15.625 μg/mL, H2 MIC: S. epidermidis ATCC 49461 strains among the tested microorganisms.Conclusion:In our study, it was determined that two different commercial Hardaliye products contained very low concentrations of phenolic compounds compared to the data in the literature, and therefore it was thought that tested Hardaliye products did not show antioxidant activity.

This study compared internalized stigmatization levels of adolescents diagnosed with attention deficit and hyperactivity disorder (ADHD) with those of their parents. The study’s data were collected from 107 adolescents diagnosed with ADHD and their parents between July 2020 and March 2021. The adolescents were followed up in the child and adolescent psychiatry outpatient clinic of a university hospital in western Turkey. The information forms for adolescents and parents, the Internalized Stigma of Mental Illness Scale—Adolescent Form (ISMI-AF) and the Parental Internalized Stigma of Mental Illness Scale (PISMI), were used to collect the data. There was no statistically significant difference between the total scores of internalized stigma and subscale mean scores of the adolescents and their parents (p > 0.05); only the subscale scores for stereotype endorsement were found to be significantly different (p < 0.05). PISMI scores affected ISMI-AF scores, which can be interpreted as parents’ perspectives and attitudes toward stigmatization affecting adolescents. For ADHD, whose frequency is increasing daily, intervention studies should be conducted to reduce adolescents’ and parents’ internalized stigma and to enhance the educational outcomes of adolescents.

Objective:Diagnosis of sleep disorders (SD) and restless legs syndrome (RLS) in school-age pediatric population and finding their relevant factors are important to prevent disease dependent complications such as growth-development retardation, loss of neurocognitive function and school failure. The aim of the present study was to determine whether there is a relationship between socio-demographic characteristics, SD and RLS in school children.Materials and Methods:Middle and high school students aged between 13 and 17 were questioned about socio-demographic data, RLS survey and pediatric sleep questionnaire (PSQ).Results:The study included 3.568 appropriately completed surveys. The total PSQ score was 4.3±3.3 for female students and 3.9±3.3 for male students. PSQ score was ≥8 in 326 of 1.992 female students (16.4%), in 215 of 1.576 male students (13.6%) and in 541 of all students (15.2%). The RLS frequency was 4.4% for all students, 4.6% for female students and 4.1% for male students. Total PSQ score, snoring, sleepiness and behavior subscale score had significant correlation with RLS in both genders. A weak but significant correlation was found between PSQ total score and BMI Z score (r=0.256, p

Background and Objectives: Allergic contact dermatitis is a common type IV hypersensitivity reaction characterised by redness, itching, oedema and thickening of the skin. It occurs in about 7% of the population and its incidence is increasing. It has been observed that the preconditioning of tissues by exposing them to transient ischemia increases resistance to subsequent permanent ischemia, and this phenomenon is called ischemic preconditioning. It has been shown that conditioning in one organ can also protect other organs. The protective effect of remote ischemic preconditioning is thought to be based on the induction of anti-inflammatory responses. The aim of this project was to investigate the anti-inflammatory and antipruritic effects of remote ischemic postconditioning in a mouse model of experimental allergic contact dermatitis. Methods: Experimental allergic contact dermatitis was induced with 1-fluoro-2,4-dinitrobenzene. Remote ischemic postconditioning was performed at 3 and 25 h after the challenge. Ear thickness and number of scratches 24 and 48 h after challenge, as well as cytokine levels and the infiltration of mast cells, neutrophils, CD4+ and CD8+ T lymphocytes in serum and ear tissue at 48 h were measured to determine the effect of RIPsC. Results: Remote ischemic postconditioning decreased ear thickness, one of the symptoms of allergic contact dermatitis (p < 0.0001). It had no significant effect on the number of scratches. It reduced serum IL-17 levels (p < 0.01). It alleviated local inflammation by suppressing CD8+ T lymphocyte and neutrophil infiltration. Conclusions: It was concluded that remote ischemic postconditioning may alleviate the symptoms of allergic contact dermatitis by suppressing CD8+ T lymphocyte and neutrophil infiltration and reducing IL-17 secretion.

Objective: Cisplatin is an antineoplastic agent used in adults and children for the treatment of various malignant diseases. It can cause irreversible ototoxicity. Genistein is a phytoestrogen. Genistein functions as an antioxidant and cell cycle inhibitor by inhibiting the DNA topoisomerase and tyrosine protein kinase enzymes. The protective effect of genistein in preventing cisplatin-induced ototoxicity and levels of the oxidative stress was investigated. Methods: 32 Sprague Dawley rats were used in 4 groups (control, cisplatin, cisplatin + genistein, genistein). Otoacoustic emission measurements of the distortion product were performed on the 1st, 2nd and 5th days of the test protocol. Serum malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, total antioxidant status, total oxidant status and oxidative stress index measurements were made. Results: The hearing of the cisplatin + genistein group was found to be better than that of the cisplatin group. While the malondialdehyde, total oxidant status and oxidative stress index parameters decreased significantly in the cisplatin + genistein group compared to the cisplatin group, superoxide dismutase increased significantly (p

Objective. Colorectal cancer (CRC) is one of the most common and fatal malignancies worldwide. Although the clinical presentation varies according to the location of the tumor, hematochezia, tenesmus, changes in the defecation habit, chronic constipation, abdominal pain, and distension are the most common findings of CRCs. We aimed to investigate whether patients with CRC who had a surgical history for benign anal disease have more negative tumoral features or not. Material and Methods. Two-hundred fifty two patients who underwent surgery for CRC between 2010 and 2016 at general surgery clinic in Ankara Numune Training and Research Hospital included in this study. Patients were classified into two groups; patients who had undergone surgery for benign perianal disease such as hemorrhoid, anal fissure, perianal abscess and fistulae (Group 1) and patients without past history for perianal surgery (Group 2). Results. A total of 252 CRC patients with a mean age of 64.2 years were included in the study. There were 95 (37.7%) females and 157 (62.3%) males. There were 25 (9.9%) patients who had surgical history for benign perianal disease. There were no statistically differences in tumor size, lymph node positivity, presence of distant metastasis, and tumor stage between the groups (p > 0.05). Conclusion. Although not statistically significant, CRC patients with a history of surgery for benign perianal disease had less lymphatic metastases and tumor size than those without prior perianal surgery. We think that this finding is important in that it indicates the importance of detailed and appropriate evaluation of patients with CRC.

Background and Objectives. Skeletal muscle atrophy, a condition characterized by decreased muscle mass and contractility, is commonly observed in various pathological states, including prolonged inactivity, malnutrition, sarcopenia, and type 1 diabetes mellitus (T1DM). We aimed to investigate the potential therapeutic effects of pterostilbene (PTS), resveratrol (RSV), pulsed magnetic field (PMF), and their combinations on the streptozotocin- (STZ-) induced atrophy of slow- and fast-twitch skeletal muscles in rats. Material and Methods. Biomechanical analyses were utilized to examine the contractions of soleus and extensor digitorum longus (EDL) muscles, while muscle morphology was evaluated using hematoxylin-eosin staining. Immunohistochemical methods were employed to assess atrophy-related markers, including FBXO32, TRIM63, and FoxO3a. The levels of key proteins, such as pAkt, mTOR, FoxO3a, MSTN, CAPN3, TNF-α, NF-κB, MyHC IIb, MyLC 3, and GLUT4, in both skeletal muscle tissue and serum insulin levels were determined using ELISA. Total protein concentration was measured using the Bradford protein assay, and relative gene expressions of FBXO32, TRIM63, FoxO3a, 4E-BP1, p70S6K, TRIM72, and UbC were analyzed by real-time PCR. Results. Our findings suggest that antioxidants and PMF may alleviate impaired protein synthesis and degradation pathways in skeletal muscle atrophy. PTS showed a positive effect on the anabolic pathway, while RSV and PMF demonstrated potential for ameliorating the catabolic pathway. Notably, the combination therapy of antioxidants and PMF exhibited a stronger ameliorative effect on skeletal muscle atrophy than either intervention alone. Conclusion. The present results highlight the benefits of employing a multimodal approach, involving both antioxidant and PMF therapy, for the management of muscle-wasting conditions. These treatments may have potential therapeutic implications for skeletal muscle atrophy.

Amaç: Bu çalışmada, glioblastoma hücre hattında (U87) siklopamin ve temozolomid (TMZ) tedavisinin ayrı ayrı ve kombine olarak uygulanmasından sonra miR-20a ekspresyonunun araştırılması ve bu miRNA’nın glioblastoma tedavisindeki etkinliğinin değerlendirilmesi amaçlanmıştır. Gereç ve Yöntem: U87 MG, tedaviden önce 35 mm'lik kültür kabı üzerine yerleştirildi ve çoğaltıldı. Çalışma kapsamında 7 grup oluşturuldu: Grup 1: Kontrol grubu, Grup 2: Sham grubu (Dimetil sülfoksit), Grup 3: 2 Gün TMZ, Grup 4: 5 Gün TMZ, Grup 5: 3 saat siklopamin, Grup 6: 2 Gün TMZ + 3 saat siklopamin, Grup 7: 5 Gün TMZ + 3 saat siklopamin. Tedaviden sonra total miRNA izolasyonu ve qRT-PCR yapıldı. Bulgular: Glioblastoma hücre hattında miR-20a ekspresyonunun grup 3, grup 4, grup 5, grup 6 ve grup 7’de belirgin olarak azaldığı tespit edildi. Ancak bu azalmanın en fazla grup 7 de olduğu saptandı . Ek olarak grup 7’de hücre sayısının azaldığı görüldü. Sonuç: Glioblastoma hücrelerinde miR-20a’nın yüksek oranda eksprese olduğu; ancak siklopamin ve TMZ tedavilerinden sonra ekspresyonun azaldığı tespit edildi. miR-20a’nın glioblastoma için yeni bir terapötik hedef ve biyobelirteç olarak kullanılabileceği, siklopamin ve TMZ’nin glioblastomada tedavi amaçlı kullanılabileceği ancak bu konuda daha ileri çalışmaların yapılması gerektiği sonucuna varıldı.

Bu çalışmanın amacı Türkiye-Birleşik Krallık ilişkilerinin güvenlik ve savunma sanayi boyutunu ortaya çıkarmaktır. Çalışmanın temel iddiası, belirli bir seviyeye ulaşan siyasi ve ekonomik ilişkilerin ötesinde, gelecek dönemde Türkiye ve Birleşik Krallık ilişkilerinde güvenlik ve savunma sanayi alanının giderek daha fazla önem kazanacağı ve gelişeceğidir. Köklü tarihi ilişkilere dayanan Türkiye ve Birleşik Krallık ilişkileri son dönemde yeni bir ivme kazanmıştır. Bunun Türkiye açısından nedeni ABD ve AB ile yaşanılan sorunlar olurken, Birleşik Krallık açısından nedeni ise AB üyeliğinden ayrılması sonrası izlemeye başladığı bağımsız ve küresel dış ve güvenlik politikasıdır. Türkiye ile Birleşik Krallık arasındaki ilişkilerin siyasi ve ekonomik boyutlarının belirli bir seviyeye ulaşmasına karşın, ortaya çıkan yeni gelişmeler, güvenlik ve savunma sanayi alanında gelişime açık bir potansiyel barındırmaktadır. Günümüzde gelişmiş siyasi ve ekonomik ilişkilere sahip olan ve her ikisi de NATO üyesi olup AB üyesi olmayan Türkiye ve Birleşik Krallık güvenlik ve savunma sanayi alanlarında işbirliğini artırarak ilişkilerini daha üst seviyeye çıkarma imkânına sahiptirler.

Introduction:Disability and decrease in the quality of life owing to the nature of schizophrenia are considered factors that predispose patients to parasitic infections. This study aimed to investigate intestinal parasites in schizophrenia and healthy volunteers with similar age-gender data and to contribute to the literature and/or clinical practice by determining the underlying cause of gastrointestinal complaints (such as side effects of psychiatric drugs or overlooked parasitic infection) in patients with schizophrenia.Methods:This case-control study included 30 patients with schizophrenia and 30 healthy volunteers. Their stool samples were examined for the presence of intestinal parasites primarily microscopically or serologically in cases requiring differential diagnosis.Results:The overall positivity rate of intestinal parasites was 25% (15/60). The difference between the intestinal parasite detection rates, which was 36.7% (11/30) in the schizophrenia group and 13.3% (4/30) in the healthy control group, was significant (odds ratio: 3.76; 95% confidence interval: 1.04- 13.65; p

The ubiquitin-proteasome system is an essential regulator of many cellular processes including controlling protein homeostasis. The degradation of proteins by the multi-subunit proteasome complex is tightly regulated through a series of checkpoints, amongst which are a set of deubiquitinating proteases (DUBs). The proteasome-associated DUBs, UCH-L5 (Ubiquitin carboxyl-terminal hydrolase isozyme L5) and USP14 (Ubiquitin-specific protease 14), and the integral-DUB in the proteasome, Rpn11, is known to regulate proteasomal degradation by deubiquitination of distinct substrates. Although selective inhibitors for USP14 and Rpn11 have been recently developed, there are no known inhibitors that selectively bind to UCH-L5. The X-ray structure of the Ubiquitin (Ub) bound to UCH-L5 shows a β-sheet hairpin in Ub that contains a crucial hydrophobic patch involved in the interaction with UCH-L5. Herein, we designed and developed both a Ub sequence-based linear- and cyclic- β-sheet hairpin peptide that was found to preferably inhibit UCH-L5. We show that these peptides have low micromolar IC50 values and the cyclic peptide competes with the activity-based UbVME (Ubiquitin-Vinyl-Methyl-Ester) probe for UCH-L5, binding in a concentration-dependent manner. We further establish the selectivity profile of the cyclic peptide for UCH-L5 compared to other members of the UCH-DUB family and other cysteine DUBs in cell lysate. Furthermore, the cyclic peptide infiltrated cells resulting in the accumulation of polyUb chains, and was found to be non-toxic at the concentrations used here. Taken together, our data suggest that the cyclic peptide permeates the cell membrane, inhibits UCH-L5 by possibly blocking its deubiquitinating function, and contributes to the accumulation of polyubiquitinated substrates. The implications of inhibiting UCH-L5 in the context of the 26S proteasome render it an attractive candidate for further development as a potential selective inhibitor for therapeutic purposes.

Autophagy is a conserved cellular process involved in the degradation of intercellular materials. During this process, double-membrane vesicles called autophagosomes engulf cytoplasmic components ready for degradation. A key component in the formation of autophagosomes are the autophagy-related (Atg) proteins, including microtubule-associated protein light chain 3A (LC3A) and 3B (LC3B). After the C-terminus of LC3 is conjugated to a phospholipid, it promotes the elongation of the phagosome and provides a docking station for the delivery of proteins ready for degradation. Since dysregulation of the autophagy pathway has been associated with a variety of human diseases, components of this process have been considered as potential therapeutic targets. However, the mechanistic details of LC3-specific ligases and deconjugation enzymes are far from unraveled and chemical tools for activity profiling could aid in affording more insights into this process. Herein, we describe a native chemical ligation approach for the synthesis of two LC3 activity-based probes (ABPs). Initial studies show that the probes covalently interact with the cysteine protease ATG4B, showcasing the potential of these probes to unravel mechanistic and structural details.