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Development of silver-based hybrid nanoparticles loaded with eEF2 K-siRNA and quercetin against triple-negative breast cancer
No full textBreast cancer is the most common cancer among women, with approximately 2.3 million new cases globally. Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the lack of estrogen receptor (ER), progesterone receptor (PR), and HER2 expression, making it unresponsive to traditional therapies. Eukaryotic Elongation Factor 2 Kinase (eEF2K) is overexpressed in TNBC, promoting cell survival by inhibiting apoptosis through phosphorylation of eEF2. Recently, eEF2K has been targeted for cancer therapy, and siRNA-based gene therapy has emerged as an effective approach to silence overexpressed genes. However, siRNA delivery is challenging due to its instability and susceptibility to degradation. In this study, we developed a novel hybrid nanoparticle (HNP) using a Layer-by-Layer (LbL) method for siRNA delivery targeting eEF2K in TNBC. The HNPs consist of a silver nanoparticle (AgNP) core, coated with poly (allylamine hydrochloride) (PAH) and poly(styrene sulfonate) (PSS), and loaded with eEF2K-siRNA and quercetin (QU), a chemotherapeutic agent, in separate layers. The nanoparticles also incorporated 4-ATP molecules for Raman traceability. In vitro experiments on TNBC cell lines (MDA-MB-231, BT-549, 4T1) showed that the combination therapy of eEF2K-siRNA and QU reduced cell viability, inhibited colony formation, and suppressed cell migration. At high 120 nM of siRNA concentration, 3D spheroid disintegration, activation of apoptotic pathways, and eventual necrotic cell death were observed. The results demonstrate that the developed HNPs are non-toxic, effective, and offer potential as a theranostic platform for TNBC treatment
Synthesis, Biological Evaluation, Antiproliferative Activity, and Computational Insights of Carboxamide Derivatives: A Computational and Experimental Approach
No full textThe discovery of therapeutic agents is important for cancer treatment. Although dozens of agents have been used in cancer treatments, cancer continues to be a serious disease with a high mortality rate. There is an urgent need for the discovery of new anticancer agents, especially for the long-term treatment of prostate cancer. Thanks to the expansion of cancer-related data, we now can synthesize new therapeutic agents using biological methods. Carboxamide derivatives (5a–r compounds) were synthesized as a potential anticancer agent. Cell proliferation assays showed that they had antiproliferative activity against the human prostate cancer cell line PC3, particularly at the 25 μM dose. In summary, our findings revealed that 5g–l and 5m–r groups are effective agents against the prostate cancer cell line. In conclusion, Gaussian calculations were carried out in order to investigate carboxamide derivatives (5a–r compounds) at the B3LYP, HF, and M062X levels, using the 6–31++g(d,p) basis set. Molecular docking calculations were carried out on a variety of proteins, including the protein that is associated with prostate cancer (PDB ID: 3RUK and 3A99). Calculations using the ADME/T method are carried out in order to investigate the potential effects and reactions of these medicines on human metabolism
Comparison of ceftazidime-avibactam with other appropriate antimicrobial therapy for the treatment of OXA-48-or KPC-producing<i> Enterobacterales</i> infections in Türkiye: A multi-centre retrospective matched-cohort study
No full textObjective: Due to underrepresentation of carbapenemase-producing Enterobacterales infections in randomized controlled trials with ceftazidime-avibactam (CZA) and high cost of CZA therapy, other appropriate antimicrobial therapies (OAAT) are still being used for OXA-48- or KPC-producing Enterobacterales infections in T & uuml;rkiye. Methods: We conducted a multicentre retrospective 1:1 matched cohort study of patients who received >= 48 h of CZA or OAAT for documented OXA-48- or KPC-producing Enterobacterales infections. Patients were matched based on (1) the number of days (+/- 1 d) from the infection onset to the initiation of therapy, (2) INCREMENT-CPE score (+/- 1), (3) source of infection, (4) year of infectious episode, and (5) type of causative microorganism. Results: From 5 Turkish university hospitals, 180 patients were enrolled. Baseline characteristics were all similar between treatment groups. At the time of treatment initiation, 63.9% of patients were in the intensive care unit, 35.6% had septic shock and 41.1% required mechanical ventilation support. Thirty-day mortality occurred in 35.6% (32/90) of patients treated with CZA and in 56.7% (51/90) of those receiving OAAT regimens (P = 0.004). Twenty-one-day clinical response was seen in 50% (45/90) and 26.7% (24/90) of patients receiving CZA and OAAT, respectively (P = 0.002). In multivariable logistic regression analyses, CZA treatment was associated with less likelihood of mortality (aOR = 0.37; 95% CI: 0.19-0.71; P = 0.003) and higher likelihood of 21-d clinical response (aOR = 3.32; 95% CI: 1.68-6.53; P 001). Conclusions: Treatment with CZA is associated with more favourable clinical outcomes in treatment of OXA-48- or KPC-producing Enterobacterales infections. A randomized controlled trial is needed to confirm these results. (c) 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/
Investigation of the structural and acoustic properties of biodegradable nonwovens from chicken feathers that are environmental waste
No full textProducing multi-layer soundproofing materials by combining materials with different properties is a widely used method. The production of these types of structures utilizes the superior properties of each layer contained within the structure. This study addresses the acoustic performance of nonwoven surface structures fabricated in different thicknesses and densities using chicken feather fibres in different constructions. An impedance tube was used to determine the sound absorption and sound transmission loss values of two-layer structures of different densities and thicknesses. The results show that the influence of the layer in front or behind on the values of sound transmission losses is very limited in two-layer structures with varying densities and thicknesses. However, for the degree of sound absorption, it is important which layer is closer to the sound source. These findings are based on an analysis of multifactorial experimental data. Accordingly, the sound absorption coefficients and sound transmission loss values of all two-layer structures decrease slightly with increasing sound frequency in the frequency range of 63–200 Hz and then increase. The low-density layer on the front of the combined structure ensures better sound absorption at low and medium frequencies. As the density of the front layer increases, its ability to absorb sound decreases. It has been found that the sound absorption capacity of structures with a low density on the front and a thick layer on the back is highest
İnşaat İlerleme İzlemesi (İİİ) Kapsamında Geometrik Veri Toplama Araçları Üzerine Kıyaslamalı Bir Yaklaşım
No full textA Comparative Analysis of Yolo-based Traffic Sign Detections with a Novel Turkish Traffic Sign Dataset
No full textA Compendium Review of the Global Epidemiology of Ticks and Tick-borne Diseases: Regional Insights from Türkiye
No full textVector-borne diseases have historically posed significant threats to plants, humans, domestic animals, and wildlife, with their impact being especially pronounced in tropical and subtropical regions. Among these, tick-borne diseases (TBDs) have emerged as an increasingly critical global concern. This growing threat is largely driven by the expanding geographic range of ticks and the wide array of pathogens they transmit, including viruses, bacteria, protozoa, nematodes, fungi, and infectious prion proteins. The global cumulative economic impact of the challenges caused by ticks and TBDs contributes and exacerbates the persistence of poverty and food insecurity, particularly in resource-limited and low-income regions. This multifactorial burden is further compounded by a complex network of anthropogenic factors, including climate change, habitat fragmentation and ecological degradation, rapid urbanization, changes in agroecosystem management, the resurgence of wildlife reservoirs, and increased anthropozoonotic mobility. Additionally, long-distance and intercontinental migratory birds serve as important ecological carrier hosts, naturally facilitating the widespread distribution and geographic expansion of ixodid tick populations and their associated pathogen complexes. Exacerbating these challenges are regional conflicts, weak environmental and social governance, and rising antimicrobial resistance, which complicate prevention and control efforts of TBDs. Due to the effects of numerous anthropogenic factors-primarily global warming-the risk potential of emerging and re-emerging TBDs is increasing day by day, along with the zoogeographic distribution of ticks and the global challenges they pose. From a global epidemiological perspective, the rising incidence and prevalence of TBDs hold significant implications for both medical and veterinary disciplines. This critical status necessitates an enhanced and comprehensive understanding of ticks, particularly with regard to pivotal aspects such as their vectorial capacity and pathogen transmission dynamics. According to ixodological records, approximately a total of 1,025 tick species, including fossil species, have been reported worldwide to date. Several of these species have also been documented in Türkiye. The current tick fauna reported from seven geographical regions of Türkiye comprises a total of 58 species: 8 species from 6 genera in the family Argasidae (Argas - 2 species, Carios - 1 species, Ornithodoros - 2 species, Alectorobius - 1 species, Alveonasus - 1 species and Otobius - 1 species) and 50 species from 7 genera in the family Ixodidae (Ixodes - 17 species, Rhipicephalus - 8 species, Dermacentor - 4 species, Hyalomma - 9 species, Haemaphysalis - 8 species, Alloceraea - 1 species and Amblyomma - 3 species). Notably, the genera Hyalomma and Ixodes have been reported as the most frequently associated with human infestations in Türkiye, highlighting their epidemiological significance and potential role in the transmission of tick-borne pathogens (TBPs). Many TBDs with zoonotic characteristics have been reported globally. These include approximately 100 viral diseases-about half of which are zoonotic-as well as numerous bacterial, protozoan, filarial nematode, fungal, and prion-related pathogens, the majority of which also exhibit zoonotic potential. In recent years, molecular epidemiological studies highlight the increasing importance of emerging TBDs. In particularly, closely monitoring TBPs in wildlife-such as transmissible prion proteins in deer and rickettsial pathogens identified in mountain goats and mountain sheep-and elucidating their zoonotic potential is critically important. In addition, the ecological importance of bat-associated tick species-especially those infesting cave-dwelling bats, such as Ixodes vespertilionis, Ixodes simplex, Ixodes ariadnae, Ixodes kaiseri, and Haemaphysalis erinacei-and their role as potential vectors for emerging and reemerging TBPs should not be overlooked. Major TBDs associated with substantial global economic losses-such as Lyme borreliosis, anaplasmosis, ehrlichiosis, babesiosis, and theileriosis-also present significant epidemiological and economic challenges in Türkiye. Notably, in the Turkish context, key TBDs including babesiosis, theileriosis, anaplasmosis, and ehrlichiosis have been documented in animals across all geographical regions, leading to considerable economic impact. Crimean-Congo hemorrhagic fever in humans has been observed predominantly in Central Anatolia and the inland areas far from the Black Sea coast, with rare cases occurring in other parts of the country. Lyme borreliosis has been reported most frequently in the Marmara Region, followed by Central Anatolia and the Mediterranean Region. The global threat of TBDs directly undermines key Sustainable Development Goals, prompting international initiatives such as the World Health Organization's "small bite, big threat" campaign and the One Health approaches and the actions, which aim to reduce zoonotic disease risks through cross-sectoral collaboration. The goal is to combat emerging and re-emerging TBDs through integrated strategies that encompass human, animal, and environmental health. Innovative strategies-including tick-derived microRNAs, CRISPR/Cas9 gene-editing, transfection systems, extracellular vesicle research, and DNA-and miRNA-based vaccines-show promise for disrupting tick biology and pathogen transmission. These advances, combined with integrated tick control programs, early warning systems, global monitoring, and open data sharing, are essential for effective tick and TBD management. Addressing this complex challenge requires international cooperation, interdisciplinary research, and an "ecocentric education" approach that fosters environmental stewardship and scientific literacy. Ultimately, halting tick spread and reducing the global burden of TBDs depends on sustained commitment to One Health principles, robust governance, and investment in research, education, and capacity-building. This compendium provides an overview of ticks, their distribution, vector competence, medical and veterinary importance, tick-pathogen-host interactions, emerging TBD threats, integrated control strategies, and the economic impacts of ticks and TBDs. Vektör kaynaklı hastalıklar, tarihsel olarak bitkiler, insanlar, evcil hayvanlar ve yaban hayatı için önemli tehditler oluşturmuş ve etkileri özellikle tropikal ve subtropikal bölgelerde belirginleşmiştir. Bunlar arasında kene kaynaklı hastalıklar (KKH’lar), giderek daha kritik bir küresel endişe kaynağı haline gelmiştir. Bu büyüyen tehdit, büyük ölçüde kenelerin genişleyen coğrafi yayılımı ve virüsler, bakteriler, protozoalar, nematodlar, mantarlar ve enfeksiyöz prion proteinleri dahil olmak üzere bulaştırdıkları çok çeşitli patojenlerden kaynaklanmaktadır. Keneler ve KKH’ların neden olduğu zorlukların küresel kümülatif ekonomik etkisi, özellikle kaynakları kısıtlı ve düşük gelirli bölgelerde yoksulluk ve gıda güvensizliğinin devam etmesine katkıda bulunmakta ve durumu daha da kötüleştirmektedir. Bu çok faktörlü yük, iklim değişikliği, habitat bozulması ve ekolojik bozulma, hızlı kentleşme, tarımsal ekosistem yönetimindeki değişiklikler, yaban hayatı rezervuarlarının yeniden canlanması ve artan antropozoonotik hareketlilik gibi karmaşık bir antropojenik faktör ağı tarafından daha da ağırlaştırılmaktadır. Ek olarak, uzun mesafeli ve kıtalararası hareket eden göçmen kuşlar, önemli ekolojik taşıyıcı konaklar olarak hizmet vererek, doğal olarak ixodid kene popülasyonlarının ve ilişkili patojen komplekslerinin yaygın dağılımını ve coğrafi yayılımını kolaylaştırmaktadırlar. Bu zorlukları daha da kötüleştiren bölgesel çatışmalar, zayıf çevresel ve sosyal yönetişim ve artan antimikrobiyal direnç, KKH’ların önlenmesi ve kontrol çabalarını zorlaştırmaktadır. Başta küresel ısınma olmak üzere çok sayıda antropojenik faktörün etkileri nedeniyle, ortaya çıkan ve yeniden ortaya çıkan KKH’ların risk potansiyeli, kenelerin zoocoğrafik dağılımı ve oluşturdukları küresel zorluklarla birlikte her geçen gün artmaktadır. Küresel epidemiyolojik bir bakış açısından, KKH’ların artan insidansı ve yaygınlığı hem medikal hem de veteriner hekimliği disiplinleri için önemli sonuçlar doğurmaktadır. Bu kritik durum, özellikle vektör kapasiteleri ve patojen bulaşma dinamikleri gibi temel hususlar açısından keneler hakkında gelişmiş ve kapsamlı bir anlayışı gerektirmektedir. İksodolojik kayıtlara göre, bugüne kadar dünya çapında fosil türler de dahil olmak üzere toplam 1,025 kene türü bildirilmiştir. Bu türlerden bazıları Türkiye’den de bildirilmiştir. Türkiye’nin yedi coğrafi bölgesinden bildirilen mevcut kene faunası toplam 58 türden oluşmaktadır: Argasidae familyasından 6 cinse ait 8 tür (Argas - 2 tür, Carios - 1 tür, Ornithodoros - 2 tür, Alectorobius - 1 tür, Alveonasus - 1 tür ve Otobius - 1 tür) ve Ixodidae familyasından 7 cinse ait 50 tür (Ixodes - 17 tür, Rhipicephalus - 8 tür, Dermacentor - 4 tür, Hyalomma - 9 tür, Haemaphysalis - 8 tür, Alloceraea - 1 tür ve Amblyomma - 3 tür). Özellikle Hyalomma ve Ixodes cinslerinin Türkiye’de insan enfestasyonlarıyla en sık ilişkilendirilen cinsler olarak bildirilmesi, epidemiyolojik önemlerini ve kene kaynaklı patojenlerin (KKP’ler) bulaşmasındaki potansiyel rollerini vurgulamaktadır. Dünya genelinde zoonotik özelliklere sahip birçok KKH bildirilmiştir. Bunlar arasında yaklaşık 100 viral hastalık (bunların yaklaşık yarısı zoonotiktir) ve çoğunluğu zoonotik potansiyel gösteren çok sayıda bakteriyel, protozoan, filarial nematod, fungal ve prionla ilişkili patojen bulunmaktadır. Son yıllarda moleküler epidemiyolojik çalışmalar, ortaya çıkan KKH’ların artan önemini vurgulamaktadır. Özellikle yaban hayatındaki KKP’lerin (geyiklerdeki bulaşıcı prion proteinleri ve dağ keçileri ile dağ koyunlarında tanımlanan riketsiyal patojenler gibi) yakından izlenmesi ve zoonotik potansiyellerinin açıklığa kavuşturulması kritik öneme sahiptir. Ayrıca, yarasalarla ilişkili kene türlerinin (özellikle mağaralarda yaşayan yarasaları enfeste eden Ixodes vespertilionis, Ixodes simplex, Ixodes ariadnae, Ixodes kaiseri ve Haemaphysalis erinacei gibi) ekolojik önemi ve ortaya çıkan ve yeniden ortaya çıkan KKP’ler için potansiyel vektörler olarak rolleri göz ardı edilmemelidir. Lyme borreliosis, anaplazmosis, ehrlichiosis, babesiosis ve theileriosis gibi küresel ekonomik kayıplara yol açan başlıca KKH’lar, Türkiye’de de önemli epidemiyolojik ve ekonomik zorluklara sebep olmaktadırlar. Özellikle Türkiye bağlamında, babesiosis, theileriosis, anaplazmosis ve ehrlichiosis gibi KKH’lar tüm coğrafi bölgelerden rapor edilmiş olup, büyük ekonomik kayıplara yol açmışlardır. İnsanlarda Kırım-Kongo hemorajik ateşi ağırlıklı olarak Orta Anadolu ve Karadeniz’in sahilden uzak iç kesimlerinde görülmüş olup, ülkenin diğer bölgelerinde de nadir olgular meydana gelmiştir. Lyme borreliosis en sık Marmara Bölgesi’nde bildirilmiş olup, bunu Orta Anadolu ve Akdeniz Bölgeleri takip etmiştir. KKH’ların küresel tehdidi, sürdürülebilir kalkınma hedeflerini doğrudan baltalamakta ve Dünya Sağlık Örgütü’nün “küçük ısırık, büyük tehdit” kampanyası ve sektörler arası iş birliği yoluyla zoonotik hastalık risklerini azaltmayı amaçlayan Tek Sağlık yaklaşımları ve eylemleri gibi uluslararası girişimleri teşvik etmektedir. Amaç, insan, hayvan ve çevre sağlığını kapsayan entegre stratejiler aracılığıyla ortaya çıkan ve yeniden ortaya çıkan KKH’larla mücadele etmektir. Kene kaynaklı mikroRNA’lar, CRISPR/Cas9 gen düzenleme, transfeksiyon sistemleri, hücre dışı vezikül araştırmaları ve DNA ve miRNA tabanlı aşılar gibi yenilikçi stratejiler, kene biyolojisini ve patojen bulaşmasını engellemede umut vadetmektedir. Entegre kene kontrol (EKK) programları, erken uyarı sistemleri, küresel izleme ve açık veri paylaşımı ile birleştirilen bu gelişmeler, etkili kene ve KKH yönetimi için hayati önem taşımaktadır. Bu karmaşık zorluğun üstesinden gelmek, uluslararası iş birliği, disiplinlerarası araştırma ve çevre yönetimini ve bilimsel okuryazarlığı destekleyen “ekosentrik eğitim” yaklaşımını gerektirir. Nihayetinde, kenelerin yayılmasını durdurmak ve KKH’ların küresel yükünü azaltmak; Tek Sağlık ilkelerini uygulamağa, güçlü yönetişim sergilemeğe ve araştırma, eğitim ve kapasite geliştirmeye ayrılan yatırıma bağlıdır. Bu derleme, keneler ve onların dağılımları, vektör yeterlilikleri, tıbbi ve veteriner önemleri, kene-patojen-konak etkileşimleri, ortaya çıkan KKH tehditleri, EKK stratejileri ve keneler ile KKH’ların kümülatif ekonomik etkileri hakkında genel bir bakış sunmaktadır
Postoperative nostril asymmetry after Le Fort I osteotomy: an analysis of the interplay between alar cinch sutures and intubation side.
No full textBackgroundOrthognathic surgery aims to improve jaw function and facial aesthetics through bilateral sagittal split osteotomy and Le Fort I osteotomy. Recent treatment goals emphasize careful evaluation of aesthetic outcomes, particularly in the nasolabial area, as repositioning the upper jaw can lead to significant soft tissue changes. This study investigates whether nasotracheal intubation affects nostril symmetry in patients undergoing Le Fort I osteotomy with/without cinch sutures.MethodsA retrospective analysis of adult patients (ages 18–30, ASA I-II) who underwent Le Fort I surgery with nasotracheal intubation at Erciyes University from 2012 to 2020 was conducted. Preoperative and at six months postoperative, 3D images were analyzed to measure nostril width (NW). Patients were categorized into Group I (with cinch sutures) and Group II (without cinch sutures). Soft tissue changes were assessed using the 3dMD imaging system.ResultsEighty-five patients were included. Significant changes in nostril width were observed between preoperative and six-month postoperative assessments in both groups. Right intubation led to increased right nostril diameter in both groups, while the left nostril showed significant change only in the cinch group. For left intubation, no significant changes were observed in nostril dimensions in the cinched group. The findings indicate that intubation side significantly influences nostril symmetry, particularly in cases of right nasotracheal intubation. The use of cinch sutures does not fully mitigate the widening effect, suggesting that the timing of cinch suture placement may be crucial.ConclusionThis study demonstrates that the nasotracheal intubation side may influence postoperative nostril width following Le Fort I osteotomy, particularly in patients receiving alar cinch sutures. The findings suggest that the physical presence of a nasotracheal tube during wound closure could interfere with the accurate assessment of alar base width.</p