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    Behavioral and Cognitive Consequences of Obesity in Parents and Offspring in Female and Male Rats: Implications of Neuroinflammation and Neuromodulation
    (Springer, 2022) Demir, Enver Ahmet; Gulbol-Duran, Gulay; Urhan-Kucuk, Meral; Dogan, Hatice; Tutuk, Okan; Cimen, Funda; Bayirli, Mucella
    Obesity is a rapidly growing public health concern that can create a family-wise burden. This study was aimed to investigate behavioral, cognitive, neuroinflammatory, and neuromodulatory consequences of the diet and parental obesity. Female and male Wistar albino rats were fed on either an obesogenic or standard diet for 12 weeks, beginning with weaning. Thereafter, the animals were matched and allowed to mate. Pups born to obese or normal parents received either the diet or standard chow to the same age. The obesogenic diet and/or parental obesity increased the locomotor activity in both females and males. The diet exhibited anxiolytic-like and antidepressant-like properties, and impaired short-term object memory as well as spatial memory. Interestingly, the obesogenic diet resulted in neuroinflammation only in naive animals, but not in the ones with parental obesity. BDNF, SIRT1, and p53 expressions were decreased, whereas RelN expression was increased in the brain with the diet, regardless of parental obesity. Multi-factor analyses demonstrated that the obesogenic diet is the prominent influencer of cognitive, neuroinflammatory, and neuromodulatory results while parental obesity has an effect on spatial memory, neuroinflammation, and hippocampal RelN and p53 expressions. Here, we provided supporting evidence for detrimental cognitive and neuroinflammatory consequences of early life consumption of the obesogenic diet which accompanies alterations in neuromodulatory factors. Surprisingly, the diet was found beneficial against anxiety-like and depression-like behaviors, and additionally, parental obesity was demonstrated to impair some aspects of cognitive performance which appears unrelated to neuroinflammation.
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    Genotyping, drug resistance and virulence factors of Candida species isolated from patients using long-term inhaled steroids
    (Wiley, 2021) Dikmen, Nursel; Duran, Nizami; Ay, Emrah; Cimen, Funda; Tek, Erhan
    Aims In this study, it was aimed to determine the isolation frequency and species distribution of Candida species isolated from asthmatic patients using long-term inhaled steroids. It was also aimed to determine the drug resistance patterns and the frequency of erg11, HWP1, ALS1, INT1, SAP1 PLB1 genes in isolates. Methods Genotyping of Candida strains isolated from patients and healthy control group was performed by PCR-RFLP method. Drug resistance was investigated phenotypically, and the presence of erg11 resistance genes and HWP1, ALS1, INT1, SAP1 PLB1 virulence genes were investigated by PCR method. Results C albicans was the most isolated species in steroid-using patients and healthy control groups (patients: 44.2%; control group: 30.8%). C tropicalis and C glabrata were found to have the highest rates of non-albicans Candida in patients with 17.4% and 13.77%, respectively. Azole resistance was found to be significantly higher in isolates isolated from patients compared to the control group. Similarly, the presence of erg11 resistance gene was highest in C albicans (17.65%), C glabrata (12.5%) and C tropicalis (8.3%) strains in the control group, while C parapsilosis was highest in patients. (57.1%) and C glabrata (54.2%) strains. Compared to the control group, the virulence of Candida strains isolated from the patients was found to be higher. Presence of HWP1, ALS1, INT1, SAP1 and PLB1 genes in patients were determined as 72.1%, 63.9%, 68.9%, 57.38% and 54.5%, respectively. These rates were 29.4%, 35.3%, 25.5%, 17.7% and 23.5% in the healthy control group, respectively. Conclusions In asthma patients using long-term inhaled steroids, both Isolation rates of Candida species, drug resistance rates, presence of virulence genes were found to be significantly higher in patients than in the control group. We think that this may be due to the suppression of cellular immunity by long-term steroid use.
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    New chalcone derivatives as effective against SARS-CoV-2 agent
    (Wiley-Hindawi, 2021) Duran, Nizami; Polat, M. Fatih; Aktas, Derya Anil; Alagoz, M. Abdullah; Ay, Emrah; Cimen, Funda; Tek, Erhan
    Aims Flavonoids and related compounds, such as quercetin-based antiviral drug Gene-Eden-VIR/Novirin, inhibit the protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The alkylated chalcones isolated from Angelica keiskei inhibit SARS-CoV proteases. In this study, we aimed to compare the anti-SARS CoV-2 activities of both newly synthesized chalcone derivatives and these two drugs. Methods Determination of the potent antiviral activity of newly synthesized chalcone derivatives against SARS-CoV-2 by calculating the RT-PCR cycling threshold (C-t) values. Results Antiviral activities of the compounds varied because of being dose dependent. Compound 6, 7, 9, and 16 were highly effective against SARS-CoV-2 at the concentration of 1.60 mu g/mL. Structure-based virtual screening was carried out against the most important druggable SARS-CoV-2 targets, viral RNA-dependent RNA polymerase, to identify putative inhibitors that could facilitate the development of potential anti-coronavirus disease-2019 drug candidates. Conclusions Computational analyses identified eight compounds inhibiting each target, with binding affinity scores ranging from -4.370 to -2.748 kcal/mol along with their toxicological, ADME, and drug-like properties.