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Objective(s): Using histopathological and immunohistochemical methods, we aimed to examine the dose-dependent effects of chronic caffeine consumption on the recovery of burn wounds in an in vivo rat model.Materials and Methods: Forty-five rats were randomly assigned to a high-dose group (20 mg/kg per day for eight weeks; n=15), a low-dose group (10 mg/kg per day for eight weeks; n=15), or a control group (n=15). The burn model was created in rats. The groups were separated into three subgroups (n=5) based on the day after injury (7th, 14th, or 21st day). The wound area, wound closure percentage, and histopathological and immunohistochemical reactivity were evaluated.Results: Successful wound healing was noted in rats treated with low doses of caffeine, similar to the control group. Pathology revealed low re-epithelization, low inflammation, and high granulation in the high-dose group. In addition, there was a significant difference between the control and high-dose groups regarding the immunohistochemical reactivity of αVβ3 integrin, VEGF, and MMP-9 (P

IntroductionRare and ultra-rare genetic conditions significantly contribute to infant morbidity and mortality, often presenting with atypical features and genetic heterogeneity that complicate management. Rapid genome sequencing (RGS) offers a timely and cost-effective approach to diagnosis, aiding in early clinical management and reducing unnecessary interventions. This pilot study represents the inaugural use of next-generation sequencing (NGS) as a diagnostic instrument for critically ill neonatal and pediatric ICU patients in a Turkish hospital setting.MethodsTen infants were enrolled based on predefined inclusion criteria, and trio RGS was performed. The mean age of the participants was 124 days, with congenital abnormalities being the most common indication for testing. Three patients had consanguineous parents. The mean turnaround time from enrollment to delivery of results was 169 h, with a diagnostic yield of 50%.ResultsThree patients received a definitive molecular diagnosis, impacting their clinical management. Two patients benefited from the exclusion of Mendelian conditions, leading to alternative diagnoses.DiscussionThis study demonstrates the feasibility and results of RGS in Turkish hospital settings, emphasizing the importance of timely genetic diagnosis in reducing the diagnostic odyssey for families and improving patient care. Further research is needed to evaluate the cost-effectiveness and applicability of RGS in the Turkish healthcare system for children with diseases of uncertain etiology.

Objective: The prevalence of obesity has increased over the past three decades. Proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus (ARC) play a vital role in induction of satiety. Chronic consumption of high-fat diet is known to reduce hypothalamic neuronal sensitivity to hormones like leptin, thus contributing to the development and persistence of obesity. The functional and morphological effects of a high-calorie diet on POMC neurons and how these effects contribute to the development and maintenance of the obese phenotype are not fully understood. For this purpose, POMC-Cre transgenic mice model was exposed to high-fat diet (HFD) and at the end of a 3- and 6-month period, electrophysiological and morphological changes, and the role of POMC neurons in homeostatic nutrition and their response to leptin were thoroughly investigated. Methods: Effects of HFD on POMC-satiety neurons in transgenic mice models exposed to chronic high-fat diet were investigated using electrophysiological (patch-clamp), chemogenetic and Cre recombinase advanced technological methods. Leptin, glucose and lipid profiles were determined and analyzed. Results: In mice exposed to a high-fat diet for 6 months, no significant changes in POMC dendritic spine number or projection density from POMC neurons to the paraventricular hypothalamus (PVN), lateral hypothalamus (LH), and bed nucleus stria terminalis (BNST) were observed. It was revealed that leptin hormone did not change the electrophysiological activities of POMC neurons in mice fed with HFD for 6 months. In addition, chemogenetic stimulation of POMC neurons increased HFD consumption. In the 3-month HFD-fed group, POMC activation induced an orexigenic response in mice, whereas switching to a standard diet was found to abolish orexigenic behavior in POMC mice. Conclusions: Chronic high fat consumption disrupts the regulation of POMC neuron activation by leptin. Altered POMC neuron activation abolished the neuron's characteristic behavioral anorexigenic response. Change in nutritional content contributes to the reorganization of developing maladaptations.

Abstract Norepinephrine (NE) is a well-known appetite regulator, and the nor/adrenergic system is targeted by several anti-obesity drugs. To better understand the circuitry underlying adrenergic appetite control, here we investigated the paraventricular hypothalamic nucleus (PVN), a key brain region that integrates energy signals and receives dense nor/adrenergic input, using a mouse model. We found that PVN NE level increases with signals of energy deficit and decreases with food access. This pattern is recapitulated by the innervating catecholaminergic axon terminals originating from NTSTH-neurons. Optogenetic activation of rostral-NTSTH → PVN projection elicited strong motivation to eat comparable to overnight fasting whereas its inhibition attenuated both fasting-induced & hypoglycemic feeding. We found that NTSTH-axons functionally targeted PVNMC4R-neurons by predominantly inhibiting them, in part, through α1-AR mediated potentiation of GABA release from ARCAgRP presynaptic terminals. Furthermore, glucoprivation suppressed PVNMC4R activity, which was required for hypoglycemic feeding response. These results define an ascending nor/adrenergic circuit, NTSTH → PVNMC4R, that conveys peripheral hunger signals to melanocortin pathway.

Abstract Arum elongatum has various bioactive compounds including phenolic acids and flavonoids that may have beneficial effects on human health. The main objectives of this study were to determine the phenolic profile of the A. elongatum plant together with the total phenolic (TPC), total flavonoid contents (TFC), and total antioxidant capacities of A. elongatum infusions throughout gastrointestinal digestion. The samples used in the present study were obtained from two cities (C1 and C2) in Türkiye. According to the results, while the primary compounds found in sample C1 were vanillic acid (51.29 ± 2.61 ng/mg), p‐coumaric acid (48.36 ± 2.84 ng/mg) and O‐coumaric acid (156.02 ± 0.67 ng/mg); chlorogenic acid (50.63 ± 0.65 ng/mg), scutellarin (144.34 ± 0.74 ng/mg), and O‐coumaric acid (53.34 ± 0.97 ng/mg) were the major compounds in C2 sample showing the differences between different locations. In addition to these, although both TPC and TFC values for C2 infusion (2960 ± 104 mg GAE/100 g and 397 ± 50 mg CE/100 g, respectively) were found to be higher than the infusion of sample C1, there were no significant differences between the TPC and TFC results after intestinal digestion (p > 0.05). Besides, TPC of the bioaccessible fractions of these two samples didn't show a significant difference (p > 0.05), whereas C1 infusion (202 ± 21%) presented a higher value than the C2 infusion (143 ± 12%) for their bioaccessible TFC value. Our results indicated that A. elongatum infusion may be a potential herbal tea due to its rich phenolic content, making it a suitable substitute for widely used herbal teas.

Elk-1 is a member of the ETS domain transcription factor superfamily that is phosphorylated upon mitogen-activated protein kinase (MAPK) pathway activation, which in turn regulated its interaction with partner protein serum response factor (SRF), leading to formation of a ternary complex with DNA. It has previously been reported that Elk-1 interacts with a mitotic kinase Aurora-A, although the mechanisms or the relevance of this interaction was unclear. Elk-1 was also reported to be phosphorylated by CDK5 on Thr417 residue. In this study, we show for the first time that this transcription factor interacts not only with Aurora-A but also with other mitotic kinases Aurora-B, Plk1, and Cdk1, and we define the interaction domain on Elk-1 to the first N-terminal 205 amino acids. We also describe putative phosphorylation sites of these mitotic kinases on Elk-1 and show that Elk-1 peptides containing these residues get phosphorylated by the mitotic kinases in in vitro kinase assays. We also perform bioinformatic analysis of mitotic phosphoproteomes and determine potential interaction partners for Elk-1 in Plk or Aurora phosphoproteomes. We propose that understanding the dynamic phosphorylation of Elk-1 by mitotic kinases is important and that it can present a novel target for anticancer strategies.

Summary: Opioids are generally known to promote hedonic food consumption. Although much of the existing evidence is primarily based on studies of the mesolimbic pathway, endogenous opioids and their receptors are widely expressed in hypothalamic appetite circuits as well; however, their role in homeostatic feeding remains unclear. Using a fluorescent opioid sensor, deltaLight, here we report that mediobasal hypothalamic opioid levels increase by feeding, which directly and indirectly inhibits agouti-related protein (AgRP)-expressing neurons through the μ-opioid receptor (MOR). AgRP-specific MOR expression increases by energy surfeit and contributes to opioid-induced suppression of appetite. Conversely, its antagonists diminish suppression of AgRP neuron activity by food and satiety hormones. Mice with AgRP neuron-specific ablation of MOR expression have increased fat preference without increased motivation. These results suggest that post-ingestion release of endogenous opioids contributes to AgRP neuron inhibition to shape food choice through MOR signaling.

Abstract Non-gastric upper gastrointestinal system polyps are detected rarely and mostly incidentally during upper gastrointestinal endoscopy. While the majority of lesions are asymptomatic and benign, some lesions have the potential to become malignant, and may be associated with other malignancies. Between May 2010 and June 2022, a total of 127,493 patients who underwent upper gastrointestinal endoscopy were retrospectively screened. Among these patients, those who had polyps in the esophagus and duodenum and biopsied were included in the study. A total of 248 patients with non-gastric polyps were included in this study. The esophageal polyp detection rate was 80.00/100,000, while the duodenal polyp detection rate was 114.52/100,000. In 102 patients (41.1%) with esophageal polyps, the mean age was 50.6 ± 15.1, and 44.1% (n = 45) were male. The most common type of polyps was squamous papilloma (n = 61, 59.8%), followed by inflammatory papilloma (n = 18, 17.6%). In 146 patients (58.9%) with duodenal polyps, the mean age of patients was 58.3 ± 16.5, and 69.8% (n = 102) were male. Brunner's gland hyperplasia, inflammatory polyp, ectopic gastric mucosa, and adenomatous polyp were reported to be the most prevalent types of polyps in the duodenum overall (28.1%, 27.4%, 14.4%, and 13.7%, respectively). It is crucial to identify rare non-gastric polyps and create an effective follow-up and treatment plan in the era of frequently performed upper gastrointestinal endoscopies. The epidemiological assessment of non-gastric polyps, as well as a follow-up and treatment strategy, are presented in this study.

This study was conducted to determine the occurrence, population growth, infestation and damage caused by Olive fly in olive orchards of Mardin province during 2016-2017. Pheremone traps, yellow sticky traps and beat sheet sampling were used to monitor population development and other parameters. It was observed that the first adults emerged at the end of July or beginning of August and the pest continued emerging until end of November. The pest occurred in 42.5% of the monitored orchards, with very low infestation (1.7-3.81%) and damage rate (2.4%-4.2%). The highest damage and infestation were recorded in Derik-1 area, while the lowest damage and infestation was noted in Dara orchard. The peak population development was observed during October in all orchards. Although population development varied in different years depending on temperature and humidity, Olive fly constitutes two peaks per year. The first peak appeared in September, while the latter in October. Overall, the pest had low population pressure in the monitored orchards in Mardin province. However, September and October are very critical for producers; therefore, management strategies should be opted against the pest during these months. Since olive fruits enter maturity phases during this period, these are susceptible to oviposition by the pest. Pest population could be significantly high, unless pest controlled during September and October. Yellow sticky traps combined with pheromone traps were 2-3 times more effective than Mcphail traps combined with 2% diammonium phosphate. Therefore, yellow sticky traps combined with pheromone traps will be beneficial against the pest as an effective biotechnical control strategy. [ABSTRACT FROM AUTHOR]

We explored an in silico model of muscle energy metabolism and demonstrated its theoretical plausibility. Results indicate that energy metabolism triggered by activation can capture the muscle condition, rest, or exercise, and can respond accordingly adjusting the rates of their respiration and energy utilization for efficient use of the nutrients. Our study demonstrated during exercise higher respiratory activity causes a substantial increase in exergy release with an increase in exergy destruction, and entropy generation rate. The thermodynamic analysis showed that at the resting state when the exergy destruction rate was 0.66 W/kg and the respiratory metabolism energetic efficiency was 36% and exergetic efficiency was 32%; whereas, when the exergy destroyed was 1.24 W/kg, the energetic efficiency was 58% and exergetic efficiency was 50% during exercise. The efficiency results suggest the ability of the system to regulate itself in response to higher work demand and become more efficient in terms of converting energy coming from nutrients to useable energy when the circulating medium has sufficient energy precursor.

Background: : Maternal Separation (MS) is an early life stress which has been associated with neurological, behavioral, chemical and endocrinological changes in adult life in rats and both short term and long-term mental health disturbances, notably depression in human. This study was planned as a neurodevelopmental depression model, to investigate the possible role of the NLRP3 pathway. Material and Method: : Rat pups were separated from their mothers on their second postnatal day (PND) for 4 h and were placed back in their home cage every day for 21 days. On PND23 they were randomly assigned to either the MS or the MS + imipramine group (receiving 30 mg/kg/day i.p. imipramine for 15 days). Depression-like behaviors were assessed by open field, sucrose preference, forced swimming and elevated plus maze tests. Prefrontal cortex regions were dissected to evaluate NLRP3, ASC and caspase-1 mRNA expressions. Results: : Significant decrease of total activity, sucrose preference as an anhedonia indicator, longer immobilization time in the forced swim test, increased time and the number of entries into the closed arms in elevated plus maze were found in the MS group compared to Control group, and these effects were reversed by imipramine treatment. NLRP3, ASC and caspase-1 mRNA expressions were increased with MS and this increase was suppressed with imipramine treatment. Conclusion: : MS causes depressive-like behaviors in rats and these behavioral changes may be related to the NLRP3 pathway. Imipramine treatment can prevent not only depression-like behaviors, but also neuroinflammation by suppressing NLRP3-mediated mechanisms in the neurodevelopmental depression process.

Azotça zengin, yeni nesil çevre dostu 1(3-klorofenil)-1H-tetrazol maddesi sentezlenmiş ve yapısı Tek kristal X- ışını kırınımı, 1H-NMR, Kızılötesi spektroskopisi, Diferansiyel Taramalı Kalorimetre ile karakterize edilmiştir. Crystal Explorer 17 programı kullanılarak hesaplanan 1(3-klorofenil)-1H-tetrazol kristalinin Hirshfeld yüzey analizi sonucunda moleküller arası etkileşimlerinin C...C (% 8.6), C...H (% 4.6), N...H (% 19.4), N...N (% 19.4), Cl...H (% 12.7) ve H...H (% 12.5) atomları arasında olduğu görülmüştür. Kütle kaybı, teorik hesaplamalar ve DSC cihazında ölçülen ısı dikkate alınarak termokinetik analizi yapıldığında maddenin ekzotermik bir tepkimeyle termal olarak bozunduğu ve en olası termal parçalanma ürünlerinin 3-klorofenil radikali ve tetrazol radikali olduğu belirlenmiştir. EXPLO5 V6.03 programı kullanılarak patlama hızı 4409 m/s, patlama basıncı 5.4 GPa ve oksijen dengesi -141.742 olarak hesaplanmıştır. Yapılan bu yeni azotça zengin enerjik madde çalışması ile maddenin kristal yoğunluğu, oksijen dengesi, erime noktası, ayrışma sıcaklığı, termokinetik analizi, patlama performansı (hız, basınç) gibi önemli fiziksel ve kimyasal özellikleri belirlenmiştir. Tasarlan yeni nesil enerjik madde çevre dostu maddelere alternatif bir enerjik madde örneği sunmaktadır. Bu sonuçlar, gelecekteki yeni nesil enerjik materyallerin tasarımında önemli bir hususu vurgulamaktadır.

Environmental concerns have been raised because of a garbage disposal facility (GDF) constructed near Çavuşlu Stream in Giresun, Turkey. This article proposes a fully validated ICP-MS technique to investigate the impacts of the GDF on the water quality of the stream and provide a human health risk estimation. Water sampling was carried out at four different stations and in tap water since the streamistheprimarysourceofdrinkingwaterfortheinhabitantsofthetown.Quantificationofselected toxic metals (As, Pb, Cd, Hg, Sb, Al, and Ni) in conjunction with the essential and other elements (Se, Cu, Fe, Mg, Mn, Zn, and Co) was performed by the use of the previously validated ICP-MSmethod.Oncewaterqualityindex(WQI),heavymetalpollutionindex(HPI),andheavymetal evaluation index (HEI) were computed, the health risk assessment was studied according to the US EPA’s method. Although the stations (2, 3, 4, and tap water) showed excellent water quality, station-1, which is the closest one to the facility, was classified as poor water quality. Lifetime cancer risk (LCR) was only significant both for adults and children in station-1. In addition, low risk regard-ingnon-carcinogenichealthhazardswasfoundforchildren.Theresultsindicatethatthefacilitydecreases the water quality of this stream and is possibly responsible for LCR. In conclusion, the ecological environment and human health should be protected by further monitoring the effect of the GDF on the ecological system.

The floras on the highest mountains in tropical eastern Africa are among the most unique floras in the world. Despite the exceptionally high concentration of endemic species, these floras remain understudied from an evolutionary point of view. In this study, we focus on the Carduus-Cirsium group (subtribe Carduinae) to unravel the evolutionary relationships of the species endemic to the tropical Afromontane and Afroalpine floras, aiming to improve the systematics of the group. We applied the Hyb-Seq approach using the Compositae1061 probe set on 190 samples (159 species), encompassing representatives of all genera of Carduinae. We used two recently developed pipelines that enabled the processing of raw sequence reads, identification of paralogous sequences and segregation into orthologous alignments. After the implementation of a missing data filter, we retained sequences from 986 nuclear loci and 177 plastid regions. Phylogenomic analyses were conducted using both concatenated and summary-coalescence methods. The resulting phylogenies were highly resolved and revealed three distinct evolutionary lineages consisting of the African species traditionally referred to as Carduus and Cirsium. Consequently, we propose the three new genera Afrocarduus, Afrocirsium and Nuriaea; the latter did notably not belong to the Carduus-Cirsium group. We detected some incongruences between the phylogenies based on concatenation vs. coalescence and on nuclear vs. plastid datasets, likely attributable to incomplete lineage sorting and/or hybridization.

Kutanöz lenfadenom, trikoblastomun adamantoid varyantı olarak sınıflandırılan benign adneksiyal bir deri tümörüdür. Nadir görülmekte olup ayırıcı tanıda derinin sık görülen tümörü bazal hücreli karsinom ile karışmaktadır. Patologlar için ayırıcı tanıda akılda tutulması gereken, bazal hücreli karsinom ile karışan, nadir görülen benign deri eki tümörünün histopatolojik ve immünohistokimyasal bulgularını sunduk.

Abstract PEA3 transcription factor subfamily is present in a variety of tissues with branching morphogenesis, and play a particularly significant role in neural circuit formation and specificity. Many target genes in axon guidance and cell–cell adhesion pathways have been identified for Pea3 transcription factor (but not for Erm or Er81); however it was not so far clear whether all Pea3 subfamily members regulate same target genes, or whether there are unique targets for each subfamily member that help explain the exclusivity and specificity of these proteins in neuronal circuit formation. In this study, using transcriptomics and qPCR analyses in SH-SY5Y neuroblastoma cells, hypothalamic and hippocampal cell line, we have identified cell type-specific and subfamily member-specific targets for PEA3 transcription factor subfamily. While Pea3 upregulates transcription of Sema3D and represses Sema5B, for example, Erm and Er81 upregulate Sema5A and Er81 regulates Unc5C and Sema4G while repressing EFNB3 in SH-SY5Y neuroblastoma cells. We furthermore present a molecular model of how unique sites within the ETS domain of each family member can help recognize specific target motifs. Such cell-context and member-specific combinatorial expression profiles help identify cell–cell and cell-extracellular matrix communication networks and how they establish specific connections.

Coenzyme Q10 (CoQ10) is a vital substance found throughout body. It helps convert food into energy and is eaten small amounts in foods. CoQ10 has gained great interest in recent years as a potential candidate for the treatment of various diseases. The content of CoQ10 in food samples is a crucial quality index for foods. Therefore, the development of sensitive separation and quantification method for determining the amount of CoQ10 in various samples, especially in foods, is an important issue, especially for food nutrition. In this study, a new, miniaturized monolithic column was developed and applied for the determination of CoQ10 in pistachio samples by nano-liquid chromatography (nano-LC). The monolithic column with a 50 µm i.d. was prepared by in situ polymerization using laurylmethacrylate (LMA) as the main monomer and ethylene dimethacrylate (EDMA) as the crosslinker. Methanol (MeOH) and polyethyleneglycol (PEG) were used as porogenic solvents. The final monolithic column was characterized by using scanning electron microscopy (SEM) and chromatographic analyses. The monolithic column with a 50 µm i.d. was applied to the analysis of CoQ10 in pistachio samples in nano-LC. This analytical method was validated by means of sensitivity, linearity, precision, recovery, and repeatability. The LOD and LOQ values were 0.05 and 0.48 µg/kg, respectively. The developed method using the monolithic column was optimized to achieve very sensitive analyses of CoQ10 content in the food samples. The applicability of the method was successfully demonstrated by the analysis of CoQ10 in pistachio samples.

Organisms uptake energy from their diet and maintain a highly organized structure by importing energy and exporting entropy. A fraction of the generated entropy is accumulated in their bodies, thus causing ageing. Hayflick’s entropic age concept suggests that the lifespan of organisms is determined by the amount of entropy they generate. Organisms die after reaching their lifespan entropy generation limit. On the basis of the lifespan entropy generation concept, this study suggests that an intermittent fasting diet, which means skipping some meals without increasing the calories uptake in the other courses, may increase longevity. More than 1.32 million people died in 2017 because of chronic liver diseases, and a quarter of the world’s population has non-alcoholic fatty liver disease. There are no specific dietary guidelines available for the treatment of non-alcoholic fatty liver diseases but shifting to a healthier diet is recommended as the primary treatment. A healthy obese person may generate 119.9 kJ/kg K per year of entropy and generate a total of 4796 kJ/kg K entropy in the first 40 years of life. If obese persons continue to consume the same diet, they may have 94 years of life expectancy. After age 40, Child–Pugh Score A, B, and C NAFLD patients may generate 126.2, 149.9, and 272.5 kJ/kg K year of entropy and have 92, 84, and 64 years of life expectancy, respectively. If they were to make a major recommended shift in their diet, the life expectancy of Child–Pugh Score A, B, and C patients may increase by 29, 32, and 43 years, respectively.