PubMed İndeksli Yayınlar Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/8

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Start date: 2021Publisher: search.filters.publisher.Springer

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  • Article
    Small Extracellular Vesicles in Tumor Metabolism and Immune Escape: Biomarkers and Therapeutic Opportunities
    (Springer, 2026) Ganjalikhani-Hakemi, Armita; Ghadiri, Nooshin; Ganjalikhani-Hakemi, Mazdak; Aru, Basak; Hosseini, Reza
    Metabolic reprogramming is a key characteristic of cancer. It is increasingly seen as a process influenced by ongoing communication between cells in the tumor microenvironment (TME). Small extracellular vesicles (sEVs) are 30-100 nm membrane-bound particles that tumor cells release in large amounts. These vesicles play an important role in the exchange of metabolic information. Besides proteins and nucleic acids, sEVs carry bioactive metabolites, lipids, and metabolic enzymes that can change the energy and building processes in recipient cells. Although there is growing evidence that sEVs contribute to metabolic changes, a complete understanding of how their varied contents relate to coordinated changes in metabolism across tumor, immune, and stromal areas is still lacking. In this review, we summarize recent findings showing that tumor-derived sEVs function like metabolic Trojan horses. They can trigger changes in glycolysis, accumulate lipids, and create dependencies on amino acids in recipient cells. This helps promote immune suppression, blood vessel growth, and resistance to treatment. We highlight the new idea of multi-metabolite sEV signaling as a factor in shaping the immunosuppressive environment of the TME. We also identify potential targets for intervention in sEV production, cargo loading, and cellular uptake, such as nSMase2, CD9/CD63-associated complexes, and macropinocytosis pathways. By combining insights from immunometabolism, cancer signaling, and the biology of extracellular vesicles, we propose that sEVs are not just biomarkers. They actively organize tumor metabolic systems and serve as valuable tools for precise immunology in cancer treatment.
  • Article
    Protective Effects of Lactobacillus Rhamnosus GG Against Methotrexate-Induced Oxidative Renal Toxicity
    (Springer, 2026) Yanardag, Refiye; Bayrak, Bertan Boran; Sener, Goksel; Almurad, Bade; Donmez, Muhammet Oguzhan
    Methotrexate (MTX) is commonly prescribed for various malignant and autoimmune conditions, but it can cause significant oxidative and functional impairment in renal tissue. Lactobacillus rhamnosus GG. (LGG) is a well-known probiotic with biological activities that support antioxidant balance. This study investigated the impact of LGG on MTX-induced kidney damage. Male Sprague-Dawley rats were divided into four groups: physiological saline-treated control group; a group receiving MTX alone; a group receiving MTX alongside a low dose of LGG; and a group receiving MTX alongside a high dose of LGG. MTX was administered as single dose (20 mg/kg/bw) intraperitoneally and LGG (low dose 1 x 10(9) CFU/day and high dose 5 & times; 10(9) CFU/day, respectively) orally for five days. On day six, blood and kidney samples were collected and examined for oxidative indicators, enzymatic antioxidant responses, and renal functional markers. MTX significantly increased in glomerular filtration markers in serum and elevated key indicators of oxidative stress in renal tissues. More so, MTX demonstrated to disrupt renal ionic homeostasis, such as declined sodium/potassium-ATPase, paraoxonase, and increased lactate dehydrogenase, carbonic anhydrase, xanthine oxidase, myeloperoxidase, and arginase activities. In contrast, LGG supplementation has been shown to effectively reverse all MTX-induced biochemical alterations in both serum and renal tissue. We can suggest that LGG can provide significant protection against oxidative renal toxicity induced by MTX in rats.
  • Article
    Protective Effects of L-Theanine against Bisphenol A-Induced Oxidative Stress and Gut Microbiota Disruption in Wistar Rats
    (Springer, 2026) Sener, Azize; Marzi, Mahdi; Sener, Goksel; Donmez, Muhammet Oguzhan
    Background Gut microbiota homeostasis plays a central role in maintaining intestinal redox balance and immune regulation. Bisphenol A (BPA), a widely distributed environmental contaminant, has been associated with oxidative stress, inflammatory responses, and disturbances in intestinal microbial communities. L-theanine (LTN), a bioactive amino acid naturally present in green tea, possesses well-documented antioxidant and anti-inflammatory properties; however, its potential protective role against BPA-induced intestinal injury has not been fully clarified. Methods and Results In the present study, female Wistar albino rats were randomly allocated into three groups: control, BPA (50 mg/kg/day), and BPA + LTN (100 mg/kg/day) and treated for 30 days. Oxidative stress and inflammatory responses in intestinal and colonic tissues were assessed by measuring malondialdehyde (MDA), reduced glutathione (GSH) levels and myeloperoxidase (MPO), catalase (CAT) activities. BPA exposure significantly increased MDA (p < 0.001) level and MPO (p < 0.001) activity while reducing GSH content (p < 0.001) and CAT activity (p < 0.001) compared with the control group. Compared to the BPA group, LTN treatment led to significant changes in MDA, MPO, and GSH levels in both tissues. MDA and MPO levels were significantly reduced in the intestine and colon tissues of the BPA + LTN group (p < 0.001). GSH and CAT levels were significantly increased in both the intestine and colon compared to the BPA group (p < 0.001). In addition, fecal microbiota composition was analyzed using 16 S rRNA gene sequencing, with taxonomic profiling performed at the phylum, genus and species levels. BPA exposure was associated with reduced microbial stability and compositional shifts within the gut microbiota, whereas LTN treatment partially restored microbial richness and community structure. Conclusions Collectively, these findings indicate that LTN alleviates BPA-induced intestinal oxidative stress and microbiota dysbiosis, suggesting its potential as a protective dietary compound against environmental toxicant-related intestinal injury.
  • Article
    Modulation of Brain Antioxidant Defense, Inflammation, and SIRT1 Activity by a Sunflower Oil-Based High-Fat Diet: Protective Role of L-Arginine in Rats
    (Springer, 2026) Şekerler, Turgut; Şener, Azize; Çavuşoğlu, Nuray; Doğan, Özge
    BackgroundChronic consumption of omega-6-enriched dietary fat may disturb brain redox balance and neuroinflammatory homeostasis. Among the sirtuins, sirtuin 1 (SIRT1) exerts critical neuroprotective functions by suppressing oxidative stress and inflammatory signaling; however, the impact of sunflower oil-based high-fat diets (SO-HFD) on brain SIRT1 activity has not been investigated.ObjectiveThis study aimed to investigate the effects of SO-HFD on oxidative stress parameters, inflammatory markers, and SIRT1 activity in rat brain tissue, and to evaluate the potential modulatory role of L-arginine supplementation.MethodsFour-week-old female Sprague-Dawley rats were allocated into three groups: control, SO-HFD, and SO-HFD + L-arginine. Both SO-HFD groups were fed a diet containing sunflower oil for 16 weeks; from week 10 onward, 1.5% L-arginine was supplemented in the drinking water of the SO-HFD + L-arginine group. Following the 16-week protocol, serum and brain specimens were collected. Serum biochemical parameters and adiponectin were quantified; brain homogenates were assayed for lipid peroxidation (MDA), reduced glutathione (GSH), protein thiols (protein-SH), nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha) levels, and SIRT1 activity.ResultsAlthough brain MDA levels were not significantly elevated, SO-HFD animals exhibited reduced GSH and protein-SH content together with diminished SIRT1 activity. The SO-HFD increased TNF-alpha and NO levels. L-arginine supplementation decreased MDA and increased GSH, protein-SH, and SIRT1 activity. L-arginine also suppressed TNF-alpha levels in brain tissue compared to the SO-HFD group. NO levels in the SO-HFD + L-arginine group were lower than in the SO-HFD group, though not significantly.ConclusionThese findings suggest that chronic exposure to an omega-6-dominant dietary environment disturbs redox regulation and inflammatory balance in brain tissue, accompanied by reduced SIRT1 activity. L-arginine may attenuate cerebral oxidative stress and neuroinflammation by reinforcing endogenous antioxidant mechanisms, highlighting its potential as a nutritional strategy against SO-HFD-induced brain oxidative stress.
  • Article
    Metabolic Responses to Benzoic Acid Stress and Glutamine Transport-Dependent Vulnerabilities in Escherichia Coli Revealed by NMR Metabolomics
    (Springer, 2026) Yuksektepe, Ecem; Elgin, Emine Sonay; Onat-Tasdelen, Kadriye Aslihan; Chae, Young Kee; Dogu, Eralp; Catav, Sukru Serter; Ozturkel-Kabakas, Hatice
    Benzoic acid (BA) is a widely used weak organic acid preservative with antimicrobial activity, yet the metabolic basis of its antibacterial action and the determinants of bacterial sensitivity remain incompletely understood. Here we combined growth assays with H-1 NMR metabolomics to characterize BA-induced metabolic responses in Escherichia coli BW25113 and to examine metabolic changes associated with impaired glutamine transport. Wild-type BW25113 and its BA-sensitive isogenic Delta glnP mutant, lacking the membrane-bound glutamine permease of the high-affinity GlnHPQ transport system, were exposed to sublethal BA concentrations. BA slowed growth and significantly altered the levels of 42 metabolites in the wild-type and 38 in Delta glnP, with the mutant showing stronger growth inhibition and reduced BA tolerance. Both strains exhibited metabolic changes consistent with cellular responses to oxidative and acid stress, including alterations in central carbon metabolism, lysine degradation, cysteine and methionine metabolism, pyrimidine metabolism, and one-carbon pool by folate. However, several metabolic responses differed between the two strains. In wild-type cells, BA exposure was associated with changes in glycerolipid metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism, lysine biosynthesis, glycine, serine and threonine metabolism, and purine metabolism. In contrast, Delta glnP cells showed distinct alterations in D-amino acid metabolism, arginine biosynthesis, and other carbon fixation pathways. In addition, the mutant displayed substantial baseline differences relative to the wild-type, including altered nucleotide and amino acid pools. Together, these results indicate that both BA exposure and deletion of glnP induce broad metabolic adjustments in Escherichia coli. Loss of glnP is associated with distinct metabolic states and altered responses to BA stress, highlighting the importance of glutamine transport in adaptation to weak organic acid stress.
  • Article
    Ibuprofen and Nimesulide Derivatives Selectively Induce Apoptosis in HER2-Positive Breast Cancer via Inhibition of the PLA2-COX-2-NF-κB Pathway
    (Springer, 2026) Bedir, Ipek; Cakirli, Egemen; Kucukguzel, S. Guniz; Yilmaz, Ozgur; Biliz, Yagmur; Telci, Dilek
    Background Chronic inflammation contributes to breast cancer development through the phospholipase A(2) (PLA(2))-cyclooxygenase-2 (COX-2)-nuclear factor kappa B (NF-kappa B) cascade, which regulates prostaglandin synthesis, oxidative stress, and transcription of pro-inflammatory and anti-apoptotic genes. This pathway is particularly active in HER2-positive breast cancer, promoting proliferation, invasion, and resistance to apoptosis. Non-steroidal anti-inflammatory drugs such as ibuprofen and nimesulide target COX enzymes and have shown potential in suppressing inflammation-driven tumorigenesis. In this study, we evaluated the anticancer and anti-inflammatory activity of newly synthesized, structurally modified ibuprofen and nimesulide derivatives designed to modulate PLA(2)-COX-2-NF-kappa B axis. Methods and Results Cytotoxicity was assessed in HER2-positive breast cancer cells (AU565 and SKBR3) and compared with normal dermal fibroblasts (HDF) and breast epithelial cells (MCF-12A), using WST-1 assays. Apoptosis, cell cycle distribution, caspase-3/7 activation, and ROS generation were analyzed by imaging-based assays, flow cytometry, and fluorescence methods. Gene expression of PLA2G2A and PTGS2 was quantified by qRT-PCR, and NF-kappa B translocation was analyzed by immunocytochemistry. Two ibuprofen triazole derivative (D1) and ibuprofen thioether derivative (D7) and one nimesulide derivative (D8) significantly reduced cell viability in a dose-dependent manner without affecting normal cells. These derivatives induced G(0)/G(1) arrest, caspase-3/7 activation, ROS reduction, and increased late apoptosis. Downregulation of PLA2G2A and PTGS2 expression and inhibition of NF-kappa B translocation confirmed disruption of the PLA(2)-COX-2-NF-kappa B cascade. Conclusion These findings demonstrate that structurally optimized ibuprofen and nimesulide derivatives exert dual anti-inflammatory and anticancer effects in HER2-positive breast cancer by suppressing PLA(2)-COX-2-NF-kappa B pathway and promoting apoptotic cell death.
  • Article
    Determination of the Susceptibility of Onychomycosis Agents Isolated in Sakarya to Octenidine Dihydrochloride and Hypochlorous Acid
    (Springer, 2026) Köroğlu, Mehmet; Çiftci, Ihsan Hakkı; Gül, Merve; Yağmur, Ahmet Can; Aydemir, Özlem; Kılbaş, İmdat; Erman, Gülay
    The aim of this study was to investigate the susceptibility of onychomycosis agents to octenidine dihydrochloride (OCT-D) and hypochlorous acid (HOCl) antiseptics using agar dilution, tube dilution, and flow cytometry methods. In this study, onychomycosis agents including dermatophytes (Trichophyton spp., Microsporum spp., Candida spp.) and secondary agents such as Aspergillus niger and Fusarium solani were cultured on Sabouraud dextrose agar (SDA). Species identification was confirmed using MALDI-TOF MS. The minimum inhibitory concentration (MIC) values of OCT-D, HOCl, and terbinafine for dermatophytes grown on culture plates were determined using the agar dilution method and the broth microdilution (tube dilution) method in accordance with the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. Following MIC determination, the minimum fungicidal concentration (MFC) was assessed. Based on the MFC results, flow cytometry analysis was performed using SYTO 9 and propidium iodide (PI) dyes to investigate the fungicidal effects of OCT-D, HOCl, and terbinafine.As a result of antifungal susceptibility testing of onychomycosis agents, approximate MIC values obtained by the agar dilution method were 250 mg/L for OCT-D, 128 mg/L for HOCl, and 0.064 mg/L for terbinafine. Using the tube dilution method, approximate MIC values were 62.5 mg/L, 64 mg/L, and 0.032 mg/L for OCT-D, HOCl, and terbinafine, respectively. Flow cytometry-based viability analyses showed that the results obtained using the tube dilution method were more consistent. Since OCT-D and HOCl demonstrated MIC values far below their commercially available concentrations and exhibited high fungicidal activity, further studies suggest that these agents may be strong alternatives for topical treatment.
  • Article
    The Relationship Between Spiritual Well-Being, Resilience, and Adherence Among Patients Receiving Hemodialysis Treatment in Türkiye
    (Springer, 2026) Bulbul, Elif; Sukut, Ozge; Dikec, Gul
    This study examined the relationship between spiritual well-being, resilience, and adherence of hemodialysis patients and the factors affecting them. The data were collected from 182 hemodialysis patients receiving treatment in a dialysis center who met the inclusion criteria by purposive sampling method in Istanbul. The data were collected with the patient description questionnaire, which measures patient sociodemographic characteristics and characteristics related to the medical diagnosis, the Spiritual Well-Being Scale, the Brief Resilience Scale, and the End-Stage Renal Failure-Adherence Questionnaire. Gender, educational status, employment status, and mean age of patients were found to be correlated with psychological resilience. Marital status, employment status, cohabitants, and mean age of patients were found to be correlated with spiritual well-being. Gender, number of weekly dialysis sessions, and dialysis competencies were found to be correlated with hemodialysis patients' adherence to their treatment. Hemodialysis patients' adherence was positively correlated with both the faith subscale of spiritual well-being and psychological resilience. According to regression analysis, gender and resilience explained 12.8% of the total variance of adherence. This study determined that resilience is an essential factor in increasing the adherence of hemodialysis patients.
  • Article
    Advances and Strategies in Biosensor-Based Diagnostics for Parasitic Infections: A Comprehensive Scoping Review
    (Springer, 2026) Aminizadeh, Selva; Alizadeh, Gita; Alizadeh, Zahra; Khalilzadeh, Balal; Abidin, Zurina Zainal; Marzi, Mahdi; Rafiei-Sefiddashti, Raheleh
    Parasitic diseases are among the most widespread infections worldwide, causing millions of deaths and illnesses each year. So rapid and accurate diagnosis is essential, requiring highly sensitive and specific tests. Biosensors can provide significant advantages over traditional diagnostic methods because of their specificity, sensitivity, speed, simplicity, ease of use, repeatability, and capacity for early-stage disease detection. Recent advances in modern diagnostic tools for detecting parasitic infections use nanomaterials such as gold nanoparticles, carbon nanofibers, and carbon nanotubes. These developments have significantly lowered detection limits to the picogram and femtogram levels. This review will cover recent advancements in biosensor-based diagnostic techniques in parasitology.
  • Article
    Citation - WoS: 2
    Citation - Scopus: 1
    Comprehensive Bibliometric Analysis of Characteristics, Patterns, and Causes of Retractions in Pediatric Literature
    (Springer, 2025) Abo-Elnour, Dina Essam; Helal, Mohamed Mohsen; Albalasy, Abdulrahman Ahmed; Abdul-Hafez, Hamza A.; Abdelkader, Ahmed; El-Sherbini, Eman Raafat; Amer, Samar A.
    This study aimed to systematically identify the key characteristics of retracted articles in pediatric literature and explore the patterns and reasons of pediatric retraction from 1995 to 2024. We searched PubMed and Retraction Watch databases to identify all retracted publications in the field of pediatrics. After the screening process, data were extracted into Excel. Statistical analysis was conducted using Jamovi and Excel. A correlation matrix was used for the important retraction-related factors. After screening, 590 unique retracted pediatric articles were included, with most of them, 572 (96.9%), having retraction notices available; 516 (87.5%) published as open access; 433 (73.4%) from Asia-mostly China; 348 (59%) retracted by the publisher; 301 (51.0%) published by Hindawi; 275 (46.6%) observational studies; and 221 (37.5%) retracted due to misconduct. Articles with four authors showed the highest retraction rate, and the retraction rate generally decreased as the number of authors increased. Most retractions occurred in 2023. The most common pediatric age group included in the retracted papers was children. The median H-index of authors of retracted papers was 8 for first authors and 10 for senior authors. The median time from submission to acceptance of retracted papers was 50 days and that from publication to retraction was 15 months. Additionally, time to retraction was positively correlated with the journal's impact factor (r = 0.106, p = 0.015) and the citation count (r = 0.213, p < 0.001) but showed no significant correlation with time to acceptance (r = - 0.019, p = 0.675). Conclusion: The increasing number of retracted pediatric papers reflects a growing concern with a complex pattern and various determinants. Researchers and publishers should adopt strong regulations and guidelines to improve the integrity of scientific research, especially pediatric research.